Dear colleagues,

We are pleased to announce the publication of GIAD Volume 3 Issue 3. This is the first special issue of GIAD, which has been edited by Professor Xiaochun Yu of West Lake University.

Below, we provide brief summaries of the published articles.

1.MRE11-RAD50-NBS1-CtIP: one key nuclease ensemble functions in the maintenance of genome stability | Tao Zhang, Zenan Zhou, Han Yang & Weibin Wang

DNA double-strand break repair is a complex process involving the MRE11-RAD50-NBS1 (MRN) complex. In this review, Assistant Professor Weibin Wang (Peking University) and colleagues explain how MRN and CtIP work together to form the MRN-CtIP nuclease complex. Professor Wang et al. then explain how this complex in turn regulates DNA damage repair and maintains genome stability. They also outline the various post-translational modifications that occur to MRN and CtIP to modulate their activity.

Fig. 1 Assembly of the MRN-CtIP complex

DNA双链断裂损伤修复是一个十分复杂的过程， 已有的研究表明，MRE11-RAD50-NBS1 (MRN)复合物在DNA损伤修复过程中发挥重要的作用。在这篇综述里，来自北京大学的王维斌助理教授团队向我们介绍了MRN与CtIP结合，形成MRN-CtIP核酸酶复合物，进而发挥DNA损伤修复作用，维持基因组稳定，同时还介绍了影响 MRN 和 CtIP的各种翻译后修饰。帮助我们更好的了解DNA损伤修复领域的最新进展。

王维斌助理教授

全文链接：https://link.springer.com/article/10.1007/s42764-022-00065-2

2.DNA-PKcs post-translational modifications and associated diseases| Zongpei Guo, Ping-Kun Zhou & Teng Ma  

DNA-PK is a holoenzyme that is formed by the binding of the DNA-dependent protein kinase catalytic subunit to the Ku70/Ku80 heterodimer. This holoenzyme has an important role in mediating of DNA double-strand break (DSB) repair. In this review, Professor Teng Ma and colleagues outline the various DNA-PKcs post-translational modifications (PTMs), their corresponding functions and roles in related diseases. They then give their insight into the latest developments in this interesting field.  

Fig. 2 Post-translational modifications of DNA-PKcs and their corresponding functions

DNA-PK是DNA依赖性蛋白激酶催化亚基与Ku70/Ku80异二聚体结合形成的一个全酶，在DNA双链断裂 (DSB)损伤修复过程中起重要作用。在这篇综述里，来自北京胸科医院肿瘤研究中心的马腾教授与北京放射医学研究所的周平坤教授向我们介绍了DNA-PKcs常见的各种翻译后修饰（PTMs）及对应的功能和相关疾病，帮助我们更好地了解DNA-PK在DNA损伤修复过程中的重要作用及相关疾病。

马腾教授

周平坤教授

全文链接：https://link.springer.com/article/10.1007/s42764-022-00073-2

3.The impact of TOPBP1 mutations in human cancers on the DNA damage response| Zhenzhen Yan, Xiuling Ge, Jiaxu Wang, Feng Xu, Mengyao Li, Xiuhua Liu, Xiaochun Yu & Chen Wu 

TOPBP1 (Topoisomerase IIβ-binding protein 1) helps to regulate the DNA damage response and maintain genome integrity. In this study, Prof. Chen Wu and colleagues describe their analysis of 369 TOPBP1 variants in 31 types of human cancers from three databases. Through their analysis, they found six TOPBP1 truncation mutations that impaired its ability to repair DNA lesions and activate the DNA damage checkpoint. They also detected 10 missense mutations that impaired TOPBP1 recruitment to DNA damage sites. These mutations therefore disrupt the DNA damage repair capacity and cell cycle arrest in G2/M phase. Through structural modeling, the researchers also found that missense mutations in TOPBP1 that alter the local spatial structure, may also affect TOPBP1 function in the DDR. Together, these findings reveal functional deficits in cancer-associated TOPBP1 mutations in the DDR, suggesting that TOPBP1 and related genes might serve as novel therapeutic targets for cancer therapy.

Fig. 3 Schematic of 10 representative missense mutations in TOPBP1

TOPBP1（拓扑异构酶IIβ结合蛋白1）在调控DNA损伤反应和维持基因组稳态起重要作用。来自河北大学的吴琛教授、刘秀华教授和西湖大学的俞晓春教授分析了来自三个数据库的31种人类癌症的369种TOPBP1变体，发现TOPBP1的6个截短突变损害了其修复DNA损伤和激活损伤检查点的能力，10个错义突变损害了TOPBP1向DNA 损伤位点的募集，从而破坏G2/M期的DNA损伤修复能力和细胞周期停滞。通过结构建模，他们还发现TOPBP1的错义突变，会改变局部空间结构，可能会影响TOPBP1在DDR中的功能。该研究揭示了DDR 中癌症相关TOPBP1突变的功能缺陷，提示TOPBP1及相关基因可能可以作为癌症治疗的新治疗靶点。

刘秀华教授

吴琛教授

俞晓春教授

全文链接：https://link.springer.com/article/10.1007/s42764-022-00072-3

4.Centrosome, microtubule and DNA damage response | Dingwei Li, Xiuwen Liu & Qiang Chen

Microtubules and centrosomes serve as transport vehicles for various proteins and major microtubule organizing centers. However, they also have an important role in regulating the DNA damage response (DDR). In this review, Prof. Qiang Chen from Wuhan University and his colleagues summarize recent advances in understanding the connection between centrosomes, microtubules, and the DDR. They also explain how cells coordinate the DDR and microtubule dynamics to facilitate double strand break (DSB) repair.

Fig. 4 Microtubule-mediated regulation of DSB dynamics

作为各种蛋白质的运输工具和主要的微管组织中心，微管和中心体对DNA损伤反应（DDR）具有重要的调控作用。在这篇综述里，来自武汉大学的陈强教授和他的同事向我们总结了中心体、微管和 DDR 之间的关联，以及细胞如何协调 DDR 与微管动力学以促进 DSB 修复的最新进展。

陈强教授

全文链接：https://link.springer.com/article/10.1007/s42764-022-00068-z

5.DNA damage accumulation in aging brain and its links to Alzheimer’s disease progression | Han Zhao, Shiyao Wang & Xu Li

DNA damage is closely related to a wide spectrum of diseases. In this review, Dr. Xu Li (Westlake University) and colleagues outline how DNA damage in the brain is associated with Alzheimer's disease (AD). They also explain how the absence of repair mechanisms can accelerate the progression of age-related AD, helping us to better understand AD pathogenesis.

Fig. 5 DNA damage repair pathways and their potential relationship with AD

DNA损伤与各种疾病密切相关。在这篇综述里，来自西湖大学的李旭教授向我们介绍了大脑中DNA损伤如何与阿尔茨海默病相关，以及修复机制的缺失如何加速与年龄相关的阿尔茨海默病的进展，帮助我们更好的了解阿尔茨海默疾病的发病机制以及制订治疗策略。

李旭博士

全文链接：https://link.springer.com/article/10.1007/s42764-022-00069-y