DNA damage mediated by UV radiation and relative repair mechanisms in mammals
Review Article
Genome Instability & Disease 3, 331–337 (2022)
Abstract
Ultraviolet (UV) radiation is one of the major environmental pathogenic factors for mammals and has been identified as a carcinogen for initiating and promoting human skin cancers. As the main chromophore for UV energy, DNA is the direct target and generates abundant photolesions, cyclobutene pyrimidine dimers (CPDs) and pyrimidine–pyrimidone (6–4) photoproducts (6–4PPs). The formation of CPDs and 6–4PPs is sequence specific and di-pyrimidine site is identified as the hotspots. Besides, some epigenetic regulations are involved in this process to influence the yield of photolesions. Upon UV radiation, the photolesions contribute to cell death and are the primary source of mutagenicity. To defend these detrimental effects to cells, DNA repair mechanisms and several signaling transduction pathways are collaborated to remove those photolesions. Nucleotide excision repair (NER) is the prominent way to recognize the damaged sites, excising the photolesions and repairing the DNA strand. Other cell responses have been along with NER system to complete the repair genetically. This review is focused on UV-induced DNA damage and summarizes current advances about the formation of CPDs and 6–4PPs as well as NER system and collaborated cell responses.
Introduction
Integrity of genome under genotoxic stress is vital for maintaining regular growth and development in all kinds of mammal organism (Lukas et al., 2011). Cells are always exposed to these exogenous or endogenous agents, like ultraviolet (UV), ionizing radiations, cisplatin and so on. The defense mechanisms are triggered by the activation of DNA damage responses and subsequent cascade signaling of DNA damage repair, cell cycle arrest to protect cells from these genotoxic dangers. However, still the intricate mechanisms of DNA damage and its repairing associated signaling pathways in different context are poorly understood.
Solar UV radiation is a strong and inevitable genotoxic stressor for all living things on the earth. It is divided into three bands according to their wavelengths, namely UVA (320–400 nm), UVB (280–320 nm), and UVC (< 280 nm). The energy of UV radiation increases along with the decrease of its wavelength. The majority UV reaching the surface of the earth consists of 95% UVA and 5% UVB, while UVC is almost kept out by ozone layer in the atmosphere. DNA is one of the key targets of UV radiation (Schuch et al., 2017). Once irradiated, the photons are absorbed directly by DNA, which is the main chromophore for sunlight. The absorption is more efficient on the band of UVB than that of UVA. Thus, UVB is generally regarded as the band with the most bioactivity UV radiation. Most studies in regard to UV-induced DNA damage has taken UVB as the source. In this review, we emphasized the current advances on UV irradiation-mediated DNA damage and its repair mechanisms as well as the relative biological responses.
UV-induced DNA damage
UV photons are absorbed by DNA, which brings about two major classes of DNA lesions, cyclobutene pyrimidine dimers (CPDs) and pyrimidine–pyrimidone (6–4) photoproducts (6–4PPs) (Schreier et al., 2015). Both of these photoproducts are based on covalent bond formation between two adjacent pyrimidine bases on the same strand (Perdiz et al., 2000). In the process of 6–4PPs production, oxetane or azedine intermediates are formed in the condition of two thymine and the connection takes place between C5–C6 double bond of 5′ base and C4 of 3′ base (Giussani et al., 2013; Yokoyama & Mizutani, 2014). CPD is a four-membered ring connecting C5 and C6 bases by a cycloaddition reaction (Zavala et al., 2014). These DNA lesions both contribute to the distortion of DNA helix. CPDs induce a bend of 7–9° on DNA helix (Sinha & Hader, 2002). 6–4PPs are more disruptive with a kink of 44° (Kim et al., 1995). Besides, ROS produced from UVB or UVA radiation selectively oxidize guanine to form specific DNA adducts, 8-OXO-7,8-dihydroguanine (8-oxoG), which leads to G–T or G–A transversions if unrepaired (Cadet et al., 2015). Due to the low formation efficiency and the similar repair mechanisms, it will not be reviewed separately below (Cadet et al., 2015).
Under native condition, the most yield class of these DNA lesions is CPDs. UV radiation triggers an increase production of CPDs and 6–4PPs, comprising 75% and 25% respectively. The induction of these photoproducts is not restricted to UVB radiation. There are plenty evidence supporting the presence of CPDs and 6–4PPs by UVC and UVA irradiated (Ikehata et al., 2015; Lawrence et al., 2018; Snellman et al., 2003; Sproul et al., 2014). The formation of CPD exposed to broadband UVB (BB-UVB) were higher compared with that exposed to narrowband UVB (NB-UVB) (Toriyama et al., 2021). But this appearance seem to be negative for skin from psoriasis patients (Snellman et al., 2003). In human keratinocytes and fibroblasts exposed to UVA, the yield of CPDs is higher than the oxidized DNA 8-oxodGuo (Courdavault et al., 2004; Mouret et al., 2006). UVC produce more absolute molecular amounts of photolesions than the same dose of UVB in mice skin through calibrating UV-damaged DNA and absolutely quantifying (Ikehata et al., 2018).
The distribution of UV-induced CPDs and 6–4PPs is not random. By chromatographic quantification methods, there is a tendency of UVB-induced damage sites presenting more frequently at di-pyrimidine sites containing cytosine, which is the photoproduct “hotspots” (Elliott et al., 2018; Jiang et al., 2021; Zavala et al., 2014). The most frequent sites are at 5′-TT and 5′-TC, and less frequent site are at 5′-CT and 5′-CC (Douki, 2013; Douki & Cadet, 2001). The specific sequence for photolesions has been revealed by several studies. Murray V and colleagues proposed that a nucleotide sequence of 5′-GCTC*AC is the consensual sites of 6–4PPs formation, and 5′-TCTT*AC is for CPDs (Chung & Murray, 2018). Soon after that they focused two conserved tetranucleotide DNA sequences, 5′-YTC*Y for the highest intensity UV-induced 6–4PP adduct and 5′-YTT*C for CPDs based on their data from end-labeling and a linear amplification/polymerase stop assay (Khoe et al., 2018). Douglas E. Brash and colleagues termed a motif sequence of 5′ yYYTTCCg/t according to adduct-Seq from UVC-irradiated fibroblasts (Premi et al., 2019). To date it is uncertain whether a specific nucleotide sequence is applicable to different cell types or different exposure situations, due to lack of more extensive experiments and is very difficult to judge whether cell specificity exists or not, due to lack of more extensive experiments.
Besides the sequence specificity, CPDs and 6–4PPs are modulated by some epigenetic mechanisms, like DNA modification, chromatin states, and transcription factors. The negligible role of DNA methylation has been discovered over the last decade. CpG methylation resulted in a decrease of CPDs and 6–4PPs following UVB and UVC irradiated to purified DNA (Leung & Murray, 2021). However, the methylation of a specific site contributes to a different effect. The mutant status of FMR1 gene in fragile-X syndrome male fibroblasts or female with inactive X chromosome results in the methylation and showed more CPDs. Cytosine methylation increases the formation of CPD regardless of the differences in UVB light sources, but no changes seen in UVC radiation (Rochette et al., 2009). 5-Hydroxymethylcytosine (5hmC), an oxidation product of 5mC, did not enhance the formation of CPDs, whereas its modified form 5-carboxylcytosine (5caC) promoted an increased level of CPDs (Kim & Pfeifer, 2021; Kim et al., 2013). Methylation at C5 improved the frequency of CPD formation, and methylation at N4 increased 6–4PPs (Douki et al., 2015). The binding of transcriptional factors with DNA protect transcriptional relative elements from photodamages even though the reduced DNA bounding at transcription start sites (TSS) remain controversial (Mao et al., 2016; Zavala et al., 2014). No significant discrepancy of CPD locations has been detected in genic and intergenic regions, which is validated in human chromosomes 1 and 6 by a CPD-specific DNA immunoprecipitation (Zavala et al., 2014). CPD hotspots are enriched at repeat elements, especially SINE element. In the regions of Alu elements which position global nucleosome in the human genome, there are 73% more CPD hotspots enriched (Zavala et al., 2014). The formations of CPD disturbed the interaction between DNA and histones enhancing the accessibility of chromatin and nucleosome rearrangement. Nucleosome rotational setting is strongly associated with the formation of CPDs (Horikoshi et al., 2016; Mao et al., 2016).
The mutagenicity of photoproducts
UV-induced DNA damage is involved in multiple biological processes, including cell apoptosis and cell senescence (Deshmukh et al., 2017; Dubois et al., 2016; Panich et al., 2016). As UV is the main environmental pathogenic factor of skin cancers, it is of great importance to elaborate the connection of photoproduct frequency to the mutant hotspots, which has been confirmed in numerous studies (Drouin & Therrien, 1997). Deficiencies of DNA repair result in xeroderma pigmentosum, patients with which are extremely sensitive to sunlight exposure and prone to develop skin cancers compared to normal people (Lambert & Lambert, 2015; Nasrallah et al., 2021). In mammal cells, CPDs possess a stronger mutagenicity than 6–4PPs, which is validated through mutant quantitative evaluation with a specific photolyase imported (You et al., 2001). CPD quantifying at di-pyrimidine sites from hot oncogenes by ligation-mediated PCR are also the frequently mutant sites in skin cancers (Bastien et al., 2013). By mapping UVB-induced CPDs, the specific sequence of cytosine deaminated CPDs are matched to the dominating mutant pattern in melanomas (Jin et al., 2021). The locations of UV signature mutant C to T in skin cancers are identified to be coincided with the sites of CPD (Ikehata et al., 2020). The C is easily deaminated to U or T, which leads to the C to T mutant formation (Ikehata et al., 2015). Therefore, although the mechanism of photoproduct induced mutagenicity, the mutagenic of photoproducts has been closely associated with cancer cell mutations.
The mechanisms to repair photoproducts
It has been reported that CPDs induced by chronic sub-lethal doses of UVB radiation persisted over time and gathered in the heterochromatin (Bérubé et al., 2018; Drigeard Desgarnier & Rochette, 2018). To maintain the integrity of the genome and convey accurate genetic information, some repair mechanisms are enabled to clear these photolesions. On account of the absence of photolyases in most mammals, the repair mechanisms below are concentrated on excision repair. There are two major repair mechanisms involved in UV radiation-induced DNA damage, base excision repair (BER) and nucleotide excision repair (NER). In UV-irradiated cells, BER is to remove base lesions oxidized by ROS (Kassam & Rainbow, 2009). Different specific DNA glycosylases recognize and remove the damage base through cutting N-glycosidic bond (Jacobs & Schar, 2012). The remaining apurinic/apyrimidinic (AP) site is removed by an AP endonuclease and the gap is filled by DNA polymerases. Finally, DNA ligase seal the strand. The study about BER function in UV-induced DNA damage is very few.
NER is a highly conserved and complex system to remove bulky DNA adducts and is the dominating pathway to repair photolesions, involving a serial process of DNA damage recognition, DNA duplex opening, pre-incision complex assembly, and excision and repair synthesis. By multiply immunological methods, UV-induced DNA lesions can be detected in just a few minutes upon UV radiation. 6–4PPs have a higher efficiency of repair than CPDs and a majority of both classes of photodamages are removed 24–48 h post UV exposure (Toriyama et al., 2021).
There are two sub-pathways for NER system: global genome NER (GG-NER) repair DNA damage among the entire genome, including regions transcriptionally active and silent; transcription-coupled NER (TC-NER) only repairs the lesions in the transcriptionally active area. In GG-NER, xeroderma pigmentosum group C(XPC) is the initial factor for sensing the damaged locations and recruiting other NER proteins. It is considered XPC recognizes lesion sites of destabilized DNA duplex other than specific DNA sequence (Scharer, 2013). But the sequence specificity to CCC/CCC mismatch has been reported by molecular dynamic and umbrella sampling simulations (Panigrahi et al., 2020). Then UV-DDB complex (DDB1/DDB2) is required to guide the lesion location by interacting with XPC. DDB2 with K244E mutant lost the capacity to incorporate lesions by single-molecule analysis (Ghodke et al., 2014). PARP binds to DDB2 and facilitated GG-NER. It also helps the recruitment of XPC in an DDB2 independent way (Robu et al., 2017). In TC-NER, RNA polymerase is responsible for DNA lesion recognition. CPDs and 6–4PPs block the transcription elongation by bringing RNA polymerase II to a halt (Duan et al., 2021).
Apart from the initial step, GG-NER and TC-NER share the similar procedures for lesion removal. XPC recruits transcriptional TFIIH complex to the damaged locations. It has been discovered that XPC binds to the subunit p62 of TFIIH complex through pleckstrin homology domain (Okuda et al., 2015). TFIIH complex is responsible to unwind the duplex due to the ATPase activities of XPB and XPD (Park et al., 2021; Zhu et al., 2012). The incision complex assembly completes when XPA, RPA, and XPG are recruited and XPC is disassociated from the damage sites. The 5′ incision is performed by XPF-ERCC1, which is recruited by XPA, and the 3′ is by XPG (Sabatella et al., 2021). Ultimately, repair synthesis is triggered and the nick is sealed through DNA polymerases and DNA ligases, which have impact on the removal efficiency of photolesions (Kemp et al., 2014). A site-specific translesion DNA synthesis (TLS) assay was performed in mouse embryonic fibroblast (MEF) cells and Pol ζ display an indispensable role in DNA synthesis extension (Akagi et al., 2020).
A number of studies have shown that the accurate regulation spatiotemporally in core NER system is of great signification. The failure of p97 extracting DDB and XPC from chromatin at the right time would raise to an unexpected genotoxicity (Puumalainen et al., 2014). In the absence of SUMOylation, the interaction between XPC and UV-DDB was excessively steady so that to a compromised NER efficiency (Akita et al., 2015). RNF111, a SUMO targeted ubiquitin ligase, promoted the dissociation of XPC from DNA (van Cuijk et al., 2015). Vitamin D receptor loss lead to the retention of XPC and reduced binding extent of XPF, altering the NER kinetics of UVC-irradiated KC (Wong & Oh, 2021).
The ubiquitination modification is vital for the proper function of NER system. It is reported that phosphorylation of XPC at serine 94 facilitated its ubiquitination and the repair rate, which is catalyzed by CK2 kinase (Shah et al., 2018). In the N-terminal tail of DDB2, there is a ubiquitinated site consisting of seven lysine for proteasome pathway. UV-DDB is interacted with Cullin4 and RBX1 to generate the ubiquitin ligase complex. XPC is ubiquitinated by interacting with DDB to enhance its binding function with DNA (Ghodke et al., 2014). Following UV exposure, endogenous DDB2 was stabilized by XPC (Matsumoto et al., 2015). USP7 is required for the repair of photolesions through XPC deubiquitylation (He et al., 2014). Besides, the deubiquitinating protein USP24 was screened as a stabilizing regulator by a yeast two-hybrid system (Zhang et al., 2012). DDB2 was also SUMOylated by SUMO E3 ligase PIASy, which lead to a delay of CPD removal (Tsuge et al., 2013).
Cell responses coupled with photodamage repair
Cell cycle distribution is usually distracted upon UV radiation exposure. The arrests at G1 and G2 phase in this situation will be helpful to repair the photolesions and refrain from inherited mutation (Pavey et al., 2001). ATR-Chk1 was activated to promote the phosphorylation of p53 by 6–4PPs via utilizing specific photolyases to eliminate the effects of photolesions (Hung et al., 2020). The crosstalk between NER and cell cycle regulation has been disclosed (Musich et al., 2017). P21 is one of the important downstream effectors of p53 and participates in cell cycle arrest following UV radiation. DDB2 promoted cell apoptosis via mediating the degradation of p21 (Li et al., 2013). There is evidence showing that p21 bond to DDB2 through PCNA interacting with PIP-box in the N-terminal of DDB2 (Cazzalini et al., 2014). The degradation of DNA replication factor CDT1 in M phase is associated with DNA replication-licensing defect (Morino et al., 2015).
DNA damage checkpoints have been studied extensively under various genotoxic stresses. Several studies reported that UV-induced DNA damage repair mechanisms, especially NER, are demonstrated to be coupled with DNA damage checkpoints. The core NER protein XPC or DDB2 deletion reduced the phosphorylation of ATM and ATR (Ray et al., 2013). Multiple signaling transduction pathways are activated when exposed to UV radiation. In NIH3T3, XPC deletion causes the reduction of p38 activation with UVC irradiated (Schreck et al., 2016). The released nucleotide in the process of NER is bond by TFIIH complex, resulting in the activation of MAPK and other relative signaling pathways (Cooke et al., 2013). In an in vitro-coupled repair-checkpoint system, the exonuclease EXO1 enlarges the gap generated by NER. The resulting ssDNA is enclosed by RPA to recruit ATR-ATRIP (Lindsey-Boltz, 2017). The double strand breaks generated depending on NER trigger the activation of ATM and subsequently its downstream MRE11 (Wakasugi et al., 2014).
Concluding remarks
As one of the most detrimental environmental factors, the effect of UV radiation on DNA damage has always raised a considerable concern. A better insight into the mechanism of the distinct DNA damage mediated by UV radiation and the associated repair system has been achieved since more high-resolution damaged omics and imaging techniques are applied. The features of photoproduct formation gradually emerge along with more specific sequencing analysis utilizing DNA damage-related omics. The rapid progress in genetics and epigenetics brings about a fighting chance to uncover the accurate operations during DNA damage formation and repair, which reveals how chromatin structure, major components (nucleosome), and functional modifications are modulated. The constant exploration of these questions will improve the comprehensive understanding of UV-induced DNA damage and its repair mechanism, which is essential for UV damage prevention and clinical treatment.
References
Akagi, J. I., Hashimoto, K., Suzuki, K., Yokoi, M., de Wind, N., Iwai, S., Ohmori, S., Moriya, H., & Hanaoka, F. (2020). Effect of sequence context on Polζ-dependent error-prone extension past (6–4) photoproducts. DNA Repair (amst), 87, 102771. https://doi.org/10.1016/j.dnarep.2019.102771
Akita, M., Tak, Y. S., Shimura, T., Matsumoto, S., Okuda-Shimizu, Y., Shimizu, Y., Nishi, R., Saitoh, H., Iwai, S., Mori, T., Ikura, T., Sakai, W., Hanaoka, F., & Sugasawa, K. (2015). SUMOylation of xeroderma pigmentosum group C protein regulates DNA damage recognition during nucleotide excision repair. Scientific Reports, 5, 10984. https://doi.org/10.1038/srep10984
Bastien, N., Therrien, J. P., & Drouin, R. (2013). Cytosine containing dipyrimidine sites can be hotspots of cyclobutane pyrimidine dimer formation after UVB exposure. Photochemical & Photobiological Sciences, 12(8), 1544–1554. https://doi.org/10.1039/c3pp50099c
Bérubé, R., Drigeard Desgarnier, M. C., Douki, T., Lechasseur, A., & Rochette, P. J. (2018). Persistence and tolerance of DNA damage induced by chronic UVB irradiation of the human genome. The Journal of Investigative Dermatology, 138(2), 405–412. https://doi.org/10.1016/j.jid.2017.08.044
Cadet, J., Douki, T., & Ravanat, J. L. (2015). Oxidatively generated damage to cellular DNA by UVB and UVA radiation. Photochemistry and Photobiology, 91(1), 140–155. https://doi.org/10.1111/php.12368
Cazzalini, O., Perucca, P., Mocchi, R., Sommatis, S., Prosperi, E., & Stivala, L. A. (2014). DDB2 association with PCNA is required for its degradation after UV-induced DNA damage. Cell Cycle, 13(2), 240–248. https://doi.org/10.4161/cc.26987
Chung, L. H., & Murray, V. (2018). An extended sequence specificity for UV-induced DNA damage. Journal of Photochemistry and Photobiology B: Biology, 178, 133–142. https://doi.org/10.1016/j.jphotobiol.2017.10.034
Cooke, M. S., Harry, E. L., Liljendahl, T. S., & Segerbäck, D. (2013). DNA nucleotide excision repair, where do all the cyclobutane pyrimidine dimers go? Cell Cycle, 12(10), 1642. https://doi.org/10.4161/cc.24701
Courdavault, S., Baudouin, C., Charveron, M., Favier, A., Cadet, J., & Douki, T. (2004). Larger yield of cyclobutane dimers than 8-oxo-7,8-dihydroguanine in the DNA of UVA-irradiated human skin cells. Mutation Research, 556(1–2), 135–142. https://doi.org/10.1016/j.mrfmmm.2004.07.011
Deshmukh, J., Pofahl, R., & Haase, I. (2017). Epidermal Rac1 regulates the DNA damage response and protects from UV-light-induced keratinocyte apoptosis and skin carcinogenesis. Cell Death & Disease, 8(3), e2664. https://doi.org/10.1038/cddis.2017.63
Douki, T. (2013). The variety of UV-induced pyrimidine dimeric photoproducts in DNA as shown by chromatographic quantification methods. Photochemical & Photobiological Sciences, 12(8), 1286–1302. https://doi.org/10.1039/c3pp25451h
Douki, T., & Cadet, J. (2001). Individual determination of the yield of the main UV-induced dimeric pyrimidine photoproducts in DNA suggests a high mutagenicity of CC photolesions. Biochemistry, 40(8), 2495–2501. https://doi.org/10.1021/bi0022543
Douki, T., Meador, J. A., Bérard, I., & Wack, A. (2015). N4-methylation of cytosine drastically favors the formation of (6–4) photoproducts in a TCG context. Photochemistry and Photobiology, 91(1), 102–108. https://doi.org/10.1111/php.12365
Drigeard Desgarnier, M. C., & Rochette, P. J. (2018). Enhancement of UVB-induced DNA damage repair after a chronic low-dose UVB pre-stimulation. DNA Repair (amst), 63, 56–62. https://doi.org/10.1016/j.dnarep.2018.01.008
Drouin, R., & Therrien, J. P. (1997). UVB-induced cyclobutane pyrimidine dimer frequency correlates with skin cancer mutational hotspots in p53. Photochemistry and Photobiology, 66(5), 719–726. https://doi.org/10.1111/j.1751-1097.1997.tb03213.x
Duan, M., Speer, R. M., Ulibarri, J., Liu, K. J., & Mao, P. (2021). Transcription-coupled nucleotide excision repair: New insights revealed by genomic approaches. DNA Repair (amst), 103, 103126. https://doi.org/10.1016/j.dnarep.2021.103126
Dubois, E. L., Gerber, S., Kisselev, A., Harel-Bellan, A., & Groisman, R. (2016). UV-dependent phosphorylation of COP9/signalosome in UV-induced apoptosis. Oncology Reports, 35(5), 3101–3105. https://doi.org/10.3892/or.2016.4671
Elliott, K., Boström, M., Filges, S., Lindberg, M., Van den Eynden, J., Ståhlberg, A., Clausen, A. R., & Larsson, E. (2018). Elevated pyrimidine dimer formation at distinct genomic bases underlies promoter mutation hotspots in UV-exposed cancers. PLoS Genetics, 14(12), e1007849. https://doi.org/10.1371/journal.pgen.1007849
Ghodke, H., Wang, H., Hsieh, C. L., Woldemeskel, S., Watkins, S. C., Rapić-Otrin, V., & Van Houten, B. (2014). Single-molecule analysis reveals human UV-damaged DNA-binding protein (UV-DDB) dimerizes on DNA via multiple kinetic intermediates. Proceedings of the National Academy of Sciences USA, 111(18), E1862-1871. https://doi.org/10.1073/pnas.1323856111
Giussani, A., Serrano-Andrés, L., Merchán, M., Roca-Sanjuán, D., & Garavelli, M. (2013). Photoinduced formation mechanism of the thymine-thymine (6–4) adduct. The Journal of Physical Chemistry B, 117(7), 1999–2004. https://doi.org/10.1021/jp307200g
He, J., Zhu, Q., Wani, G., Sharma, N., Han, C., Qian, J., Wang, Q., & Wani, A. A. (2014). Ubiquitin-specific protease 7 regulates nucleotide excision repair through deubiquitinating XPC protein and preventing XPC protein from undergoing ultraviolet light-induced and VCP/p97 protein-regulated proteolysis. Journal of Biological Chemistry, 289(39), 27278–27289. https://doi.org/10.1074/jbc.M114.589812
Horikoshi, N., Tachiwana, H., Kagawa, W., Osakabe, A., Matsumoto, S., Iwai, S., Sugasawa, K., & Kurumizaka, H. (2016). Crystal structure of the nucleosome containing ultraviolet light-induced cyclobutane pyrimidine dimer. Biochemical and Biophysical Research Communications, 471(1), 117–122. https://doi.org/10.1016/j.bbrc.2016.01.170
Hung, K. F., Sidorova, J. M., Nghiem, P., & Kawasumi, M. (2020). The 6–4 photoproduct is the trigger of UV-induced replication blockage and ATR activation. Proceedings of the National Academy of Sciences USA, 117(23), 12806–12816. https://doi.org/10.1073/pnas.1917196117
Ikehata, H., Mori, T., Douki, T., Cadet, J., & Yamamoto, M. (2018). Quantitative analysis of UV photolesions suggests that cyclobutane pyrimidine dimers produced in mouse skin by UVB are more mutagenic than those produced by UVC. Photochemical & Photobiological Sciences, 17(4), 404–413. https://doi.org/10.1039/c7pp00348j
Ikehata, H., Mori, T., Kamei, Y., Douki, T., Cadet, J., & Yamamoto, M. (2020). Wavelength- and tissue-dependent variations in the mutagenicity of cyclobutane pyrimidine dimers in mouse skin. Photochemistry and Photobiology, 96(1), 94–104. https://doi.org/10.1111/php.13159
Ikehata, H., Mori, T., & Yamamoto, M. (2015). In vivo spectrum of UVC-induced mutation in mouse skin epidermis may reflect the cytosine deamination propensity of cyclobutane pyrimidine dimers. Photochemistry and Photobiology, 91(6), 1488–1496. https://doi.org/10.1111/php.12525
Jacobs, A. L., & Schar, P. (2012). DNA glycosylases: In DNA repair and beyond. Chromosoma, 121(1), 1–20. https://doi.org/10.1007/s00412-011-0347-4
Jiang, Y., Li, W., Lindsey-Boltz, L. A., Yang, Y., Li, Y., & Sancar, A. (2021). Super hotspots and super coldspots in the repair of UV-induced DNA damage in the human genome. Journal of Biological Chemistry, 296, 100581. https://doi.org/10.1016/j.jbc.2021.100581
Jin, S. G., Pettinga, D., Johnson, J., Li, P., & Pfeifer, G. P. (2021). The major mechanism of melanoma mutations is based on deamination of cytosine in pyrimidine dimers as determined by circle damage sequencing. Science Advances. https://doi.org/10.1126/sciadv.abi6508
Kassam, S. N., & Rainbow, A. J. (2009). UV-inducible base excision repair of oxidative damaged DNA in human cells. Mutagenesis, 24(1), 75–83. https://doi.org/10.1093/mutage/gen054
Kemp, M. G., Gaddameedhi, S., Choi, J. H., Hu, J., & Sancar, A. (2014). DNA repair synthesis and ligation affect the processing of excised oligonucleotides generated by human nucleotide excision repair. Journal of Biological Chemistry, 289(38), 26574–26583. https://doi.org/10.1074/jbc.M114.597088
Khoe, C. V., Chung, L. H., & Murray, V. (2018). The sequence specificity of UV-induced DNA damage in a systematically altered DNA sequence. Journal of Photochemistry and Photobiology B: Biology, 183, 88–100. https://doi.org/10.1016/j.jphotobiol.2018.04.023
Kim, S. I., & Pfeifer, G. P. (2021). The epigenetic DNA modification 5-carboxylcytosine promotes high levels of cyclobutane pyrimidine dimer formation upon UVB irradiation. Genome Instability Disease, 2(1), 59–69. https://doi.org/10.1007/s42764-020-00030-x
Kim, J. K., Patel, D., & Choi, B. S. (1995). Contrasting structural impacts induced by cis-syn cyclobutane dimer and (6–4) adduct in DNA duplex decamers: Implication in mutagenesis and repair activity. Photochemistry and Photobiology, 62(1), 44–50. https://doi.org/10.1111/j.1751-1097.1995.tb05236.x
Kim, S. I., Jin, S. G., & Pfeifer, G. P. (2013). Formation of cyclobutane pyrimidine dimers at dipyrimidines containing 5-hydroxymethylcytosine. Photochemical & Photobiological Sciences, 12(8), 1409–1415. https://doi.org/10.1039/c3pp50037c
Lambert, W. C., & Lambert, M. W. (2015). Development of effective skin cancer treatment and prevention in xeroderma pigmentosum. Photochemistry and Photobiology, 91(2), 475–483. https://doi.org/10.1111/php.12385
Lawrence, K. P., Douki, T., Sarkany, R. P. E., Acker, S., Herzog, B., & Young, A. R. (2018). The UV/Visible radiation boundary region (385–405 nm) damages skin cells and induces “dark” cyclobutane pyrimidine dimers in human skin in vivo. Science and Reports, 8(1), 12722. https://doi.org/10.1038/s41598-018-30738-6
Leung, W. Y., & Murray, V. (2021). The influence of DNA methylation on the sequence specificity of UVB- and UVC-induced DNA damage. Journal of Photochemistry and Photobiology b: Biology, 221, 112225. https://doi.org/10.1016/j.jphotobiol.2021.112225
Li, H., Zhang, X. P., & Liu, F. (2013). Coordination between p21 and DDB2 in the cellular response to UV radiation. PLoS ONE, 8(11), e80111. https://doi.org/10.1371/journal.pone.0080111
Lindsey-Boltz, L. A. (2017). Bringing it all together: Coupling excision repair to the DNA damage checkpoint. Photochemistry and Photobiology, 93(1), 238–244. https://doi.org/10.1111/php.12667
Lukas, J., Lukas, C., & Bartek, J. (2011). More than just a focus: The chromatin response to DNA damage and its role in genome integrity maintenance. Nature Cell Biology, 13(10), 1161–1169. https://doi.org/10.1038/ncb2344
Mao, P., Smerdon, M. J., Roberts, S. A., & Wyrick, J. J. (2016). Chromosomal landscape of UV damage formation and repair at single-nucleotide resolution. Proceedings of the National Academy of Sciences USA, 113(32), 9057–9062. https://doi.org/10.1073/pnas.1606667113
Matsumoto, S., Fischer, E. S., Yasuda, T., Dohmae, N., Iwai, S., Mori, T., Nishi, R., Yoshino, K., Sakai, W., Hanaoka, F., Thomä, N. H., & Sugasawa, K. (2015). Functional regulation of the DNA damage-recognition factor DDB2 by ubiquitination and interaction with xeroderma pigmentosum group C protein. Nucleic Acids Research, 43(3), 1700–1713. https://doi.org/10.1093/nar/gkv038
Morino, M., Nukina, K., Sakaguchi, H., Maeda, T., Takahara, M., Shiomi, Y., & Nishitani, H. (2015). Mitotic UV irradiation induces a DNA replication-licensing defect that potentiates G1 arrest response. PLoS ONE, 10(3), e0120553. https://doi.org/10.1371/journal.pone.0120553
Mouret, S., Baudouin, C., Charveron, M., Favier, A., Cadet, J., & Douki, T. (2006). Cyclobutane pyrimidine dimers are predominant DNA lesions in whole human skin exposed to UVA radiation. Proceedings of the National Academy of Sciences USA, 103(37), 13765–13770. https://doi.org/10.1073/pnas.0604213103
Musich, P. R., Li, Z., & Zou, Y. (2017). Xeroderma pigmentosa group A (XPA), nucleotide excision repair and regulation by ATR in response to ultraviolet irradiation. Advances in Experimental Medicine and Biology, 996, 41–54. https://doi.org/10.1007/978-3-319-56017-5_4
Nasrallah, A., Fayyad, N., Kobaisi, F., Badran, B., Fayyad-Kazan, H., Fayyad-Kazan, M., Sève, M., & Rachidi, W. (2021). Xeroderma pigmentosum C: A valuable tool to decipher the signaling pathways in skin cancers. Oxidative Medicine and Cellular Longevity, 2021, 6689403. https://doi.org/10.1155/2021/6689403
Okuda, M., Kinoshita, M., Kakumu, E., Sugasawa, K., & Nishimura, Y. (2015). Structural insight into the mechanism of TFIIH recognition by the acidic string of the nucleotide excision repair factor XPC. Structure, 23(10), 1827–1837. https://doi.org/10.1016/j.str.2015.07.009
Panich, U., Sittithumcharee, G., Rathviboon, N., & Jirawatnotai, S. (2016). Ultraviolet radiation-induced skin aging: The role of DNA damage and oxidative stress in epidermal stem cell damage mediated skin aging. Stem Cells International, 2016, 7370642. https://doi.org/10.1155/2016/7370642
Panigrahi, A., Vemuri, H., Aggarwal, M., Pitta, K., & Krishnan, M. (2020). Sequence specificity, energetics and mechanism of mismatch recognition by DNA damage sensing protein Rad4/XPC. Nucleic Acids Research, 48(5), 2246–2257. https://doi.org/10.1093/nar/gkaa078
Park, Y. J., Kim, S. H., Kim, T. S., Lee, S. M., Cho, B. S., Seo, C. I., Kim, H. D., & Kim, J. (2021). Ribosomal protein S3 associates with the TFIIH complex and positively regulates nucleotide excision repair. Cellular and Molecular Life Sciences, 78(7), 3591–3606. https://doi.org/10.1007/s00018-020-03754-x
Pavey, S., Russell, T., & Gabrielli, B. (2001). G2 phase cell cycle arrest in human skin following UV irradiation. Oncogene, 20(43), 6103–6110. https://doi.org/10.1038/sj.onc.1204707
Perdiz, D., Grof, P., Mezzina, M., Nikaido, O., Moustacchi, E., & Sage, E. (2000). Distribution and repair of bipyrimidine photoproducts in solar UV-irradiated mammalian cells. Possible role of Dewar photoproducts in solar mutagenesis. Journal of Biological Chemistry, 275(35), 26732–26742. https://doi.org/10.1074/jbc.M001450200
Premi, S., Han, L., Mehta, S., Knight, J., Zhao, D., Palmatier, M. A., Kornacker, K., & Brash, D. E. (2019). Genomic sites hypersensitive to ultraviolet radiation. Proceedings of the National Academy of Sciences USA, 116(48), 24196–24205. https://doi.org/10.1073/pnas.1907860116
Puumalainen, M. R., Lessel, D., Rüthemann, P., Kaczmarek, N., Bachmann, K., Ramadan, K., & Naegeli, H. (2014). Chromatin retention of DNA damage sensors DDB2 and XPC through loss of p97 segregase causes genotoxicity. Nature Communications, 5, 3695. https://doi.org/10.1038/ncomms4695
Ray, A., Milum, K., Battu, A., Wani, G., & Wani, A. A. (2013). NER initiation factors, DDB2 and XPC, regulate UV radiation response by recruiting ATR and ATM kinases to DNA damage sites. DNA Repair (amst), 12(4), 273–283. https://doi.org/10.1016/j.dnarep.2013.01.003
Robu, M., Shah, R. G., Purohit, N. K., Zhou, P., Naegeli, H., & Shah, G. M. (2017). Poly(ADP-ribose) polymerase 1 escorts XPC to UV-induced DNA lesions during nucleotide excision repair. Proceedings of the National Academy of Sciences USA, 114(33), E6847-e6856. https://doi.org/10.1073/pnas.1706981114
Rochette, P. J., Lacoste, S., Therrien, J. P., Bastien, N., Brash, D. E., & Drouin, R. (2009). Influence of cytosine methylation on ultraviolet-induced cyclobutane pyrimidine dimer formation in genomic DNA. Mutation Research, 665(1–2), 7–13. https://doi.org/10.1016/j.mrfmmm.2009.02.008
Sabatella, M., Thijssen, K. L., Davó-Martínez, C., Vermeulen, W., & Lans, H. (2021). Tissue-specific DNA repair activity of ERCC-1/XPF-1. Cell Reports, 34(2), 108608. https://doi.org/10.1016/j.celrep.2020.108608
Scharer, O. D. (2013). Nucleotide excision repair in eukaryotes. Cold Spring Harbor Perspectives in Biology, 5(10), a012609. https://doi.org/10.1101/cshperspect.a012609
Schreck, I., Grico, N., Hansjosten, I., Marquardt, C., Bormann, S., Seidel, A., Kvietkova, D. L., Pieniazek, D., Segerbäck, D., Diabaté, S., van der Horst, G. T. J., Oesch-Bartlomowicz, B., Oesch, F., & Weiss, C. (2016). The nucleotide excision repair protein XPC is essential for bulky DNA adducts to promote interleukin-6 expression via the activation of p38-SAPK. Oncogene, 35(7), 908–918. https://doi.org/10.1038/onc.2015.145
Schreier, W. J., Gilch, P., & Zinth, W. (2015). Early events of DNA photodamage. Annual Review of Physical Chemistry, 66, 497–519. https://doi.org/10.1146/annurev-physchem-040214-121821
Schuch, A. P., Moreno, N. C., Schuch, N. J., Menck, C. F. M., & Garcia, C. C. M. (2017). Sunlight damage to cellular DNA: Focus on oxidatively generated lesions. Free Radical Biology & Medicine, 107, 110–124. https://doi.org/10.1016/j.freeradbiomed.2017.01.029
Shah, P., Zhao, B., Qiang, L., & He, Y. Y. (2018). Phosphorylation of xeroderma pigmentosum group C regulates ultraviolet-induced DNA damage repair. Nucleic Acids Research, 46(10), 5050–5060. https://doi.org/10.1093/nar/gky239
Sinha, R. P., & Hader, D. P. (2002). UV-induced DNA damage and repair: A review. Photochemical & Photobiological Sciences, 1(4), 225–236. https://doi.org/10.1039/b201230h
Snellman, E., Strozyk, M., Segerback, D., Klimenko, T., & Hemminki, K. (2003). Effect of the spectral range of a UV lamp on the production of cyclobutane pyrimidine dimers in human skin in situ. Photodermatology, Photoimmunology and Photomedicine, 19(6), 281–286. https://doi.org/10.1046/j.1600-0781.2003.00063.x
Sproul, C. D., Mitchell, D. L., Rao, S., Ibrahim, J. G., Kaufmann, W. K., & Cordeiro-Stone, M. (2014). Cyclobutane pyrimidine dimer density as a predictive biomarker of the biological effects of ultraviolet radiation in normal human fibroblast. Photochemistry and Photobiology, 90(1), 145–154. https://doi.org/10.1111/php.12194
Toriyama, E., Masuda, H., Torii, K., Ikumi, K., & Morita, A. (2021). Time kinetics of cyclobutane pyrimidine dimer formation by narrowband and broadband UVB irradiation. Journal of Dermatological Science, 103(3), 151–155. https://doi.org/10.1016/j.jdermsci.2021.07.009
Tsuge, M., Masuda, Y., Kaneoka, H., Kidani, S., Miyake, K., & Iijima, S. (2013). SUMOylation of damaged DNA-binding protein DDB2. Biochemical and Biophysical Research Communications, 438(1), 26–31. https://doi.org/10.1016/j.bbrc.2013.07.013
van Cuijk, L., van Belle, G. J., Turkyilmaz, Y., Poulsen, S. L., Janssens, R. C., Theil, A. F., Sabatella, M., Lans, H., Mailand, N., Houtsmuller, A. B., Vermeulen, W., & Marteijn, J. A. (2015). SUMO and ubiquitin-dependent XPC exchange drives nucleotide excision repair. Nature Communications, 6, 7499. https://doi.org/10.1038/ncomms8499
Wakasugi, M., Sasaki, T., Matsumoto, M., Nagaoka, M., Inoue, K., Inobe, M., Horibata, K., & TanakaMatsunaga, K. T. (2014). Nucleotide excision repair-dependent DNA double-strand break formation and ATM signaling activation in mammalian quiescent cells. Journal of Biological Chemistry, 289(41), 28730–28737. https://doi.org/10.1074/jbc.M114.589747
Wong, C. T., & Oh, D. H. (2021). Vitamin D receptor promotes global nucleotide excision repair by facilitating XPC dissociation from damaged DNA. The Journal of Investigative Dermatology, 141(7), 1656–1663. https://doi.org/10.1016/j.jid.2020.11.033
Yokoyama, H., & Mizutani, R. (2014). Structural biology of DNA (6–4) photoproducts formed by ultraviolet radiation and interactions with their binding proteins. International Journal of Molecular Sciences, 15(11), 20321–20338. https://doi.org/10.3390/ijms151120321
You, Y. H., Lee, D. H., Yoon, J. H., Nakajima, S., Yasui, A., & Pfeifer, G. P. (2001). Cyclobutane pyrimidine dimers are responsible for the vast majority of mutations induced by UVB irradiation in mammalian cells. Journal of Biological Chemistry, 276(48), 44688–44694. https://doi.org/10.1074/jbc.M107696200
Zavala, A. G., Morris, R. T., Wyrick, J. J., & Smerdon, M. J. (2014). High-resolution characterization of CPD hotspot formation in human fibroblasts. Nucleic Acids Research, 42(2), 893–905. https://doi.org/10.1093/nar/gkt912
Zhang, L., Lubin, A., Chen, H., Sun, Z., & Gong, F. (2012). The deubiquitinating protein USP24 interacts with DDB2 and regulates DDB2 stability. Cell Cycle, 11(23), 4378–4384. https://doi.org/10.4161/cc.22688
Zhu, Q., Wani, G., Sharma, N., & Wani, A. (2012). Lack of CAK complex accumulation at DNA damage sites in XP-B and XP-B/CS fibroblasts reveals differential regulation of CAK anchoring to core TFIIH by XPB and XPD helicases during nucleotide excision repair. DNA Repair (amst), 11(12), 942–950. https://doi.org/10.1016/j.dnarep.2012.09.003
Funding
This work was supported by grants from the National Natural Science Foundation of China (Grant No. 82103785) and the Natural Science Foundation of Guangdong Province, China (Grant No. 2020A1515110543 and 2022A1515012593). YW and MZ wrote the paper, with the assistance from XD.
Author information
Authors and Affiliations
Department of Radiation Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, China
Yinghui Wang, Xuyi Deng & Meijuan Zhou
Jiangmen Central Hospital, Affiliated Jiangmen Hospital of Sun Yat-Sen University, Jiangmen, China
Yinghui Wang
Corresponding author
Correspondence to Meijuan Zhou.
Ethics declarations
Conflict of interest
The authors declare that they have no competing interest.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Wang, Y., Deng, X. & Zhou, M. DNA damage mediated by UV radiation and relative repair mechanisms in mammals. GENOME INSTAB. DIS. 3, 331–337 (2022). https://doi.org/10.1007/s42764-022-00090-1
Received30 August 2022
Revised19 October 2022
Accepted30 October 2022
Published12 November 2022
Issue DateDecember 2022
DOIhttps://doi.org/10.1007/s42764-022-00090-1
Share this article
Anyone you share the following link with will be able to read this content:
Get shareable linkKeywords
UV radiation
DNA damage
Photoproducts
Excision repair
用户登录
还没有账号？
立即注册