Volume 3 Issue 1

1. Genotoxicity testing and recent advances | Yang Luan & Masamitsu Honma

Genotoxicity testing is performed to identify chemicals that cause genetic alterations. The data allow clinical geneticists to estimate whether a patient is at risk of carrying DNA damage. In this review, Professors Yang Luan from Shanghai Jiao Tong University (China) and Masamitsu Honma from the National Institute of Health Sciences (Japan), outline the common tests and applications of genotoxicity testing. They highlight how technological advances have helped generate next generation genotoxicity testing modalities. Finally, they explain how data from such testing is improving our understanding of the effects of environmental mutagens.

    基因毒性测试是一种识别导致基因改变的化学物质的技术。在这篇综述里，来自上海交通大学的栾洋研究员和日本国立卫生科学研究所的 Masamitsu Honma教授向我们介绍了基因毒性测试几种常见的检测与应用，帮助我们了解该领域的最新进展。

栾洋研究员：https://www.shsmu.edu.cn/sph/info/1046/1208.htm

Masamitsu Honma 教授: https://www.researchgate.net/profile/Masamitsu-Honma

全文链接：https://link.springer.com/article/10.1007/s42764-021-00058-7

2. The role of ral signaling and post translational modifications (PTMs) of Ras in cancer | Mohammad Reza Zinatizadeh, Peyman Kheirandish Zarandi, Mahsa Keshavarz-Fathi, Mohammad Hadi Yousefi & Nima Rezaei  

RAS protein is involved in many cellular processes but is particularly well known for its role in cell division and apoptosis. Unfortunately, mutations in the encoding RAS gene are common causes of cancer. For this reason, intensive research efforts have focused on understanding what regulates RAS so that we can effectively inhibit RAS signaling in cancer. In this review, Dr. Mohammad Reza Zinatizadeh from Islamic Azad University, Iran, and his colleagues present the role of Ral signaling in cancer and how it affects the post-translational modifications of RAS in health and disease. Improving our understanding of the RAS pathway is expected to open new avenues for cancer therapy.

    RAS基因是癌症调控的重要开关，近年来已有不少Ral调控RAS蛋白的报道。在这篇综述里，来自伊朗Islamic Azad大学的Mohammad Reza Zinatizadeh博士和他的同事介绍了Ral信号在癌症和Ras蛋白翻译后修饰中的作用，帮助我们更好的认识RAS通路调控，为癌症治疗提供新思路。

Mohammad Reza Zinatizadeh 博士 : https://usern.tums.ac.ir/User/CV/Zinatizadeh

全文链接：https://link.springer.com/article/10.1007/s42764-022-00059-0

3.Biological function and regulation of histone 4 lysine 20 methylation in DNA damage response| Sara Moghaddam Kohi, Tingting Feng, Yuan Tian & Wei-Guo Zhu

Histone H4K20 methylation is an essential post-translational modification (PTM) to ensure genome stability. In this review, Sara Moghaddam Kohi and colleagues summarize the roles of histone lysine methylation and its dynamics during the DNA damage response. They outline what we know so far surrounding the underlying mechanism and regulation of H4K20 methylation, and the role of this PTM in the context of DNA damage.

    组蛋白H4K20甲基化修饰是DNA损伤修复（DDR）过程中重要的翻译后修饰（PTMs）之一，对维持基因组稳定起重要作用。在这篇综述里，朱卫国教授团队向我们总结了DDR过程中H4K20甲基化及其修饰酶在DNA损伤中的功能、机制和调节，帮助我们进一步了解H4K20甲基化修饰的功能和最新研究进展。

田媛助理教授：https://med.szu.edu.cn/Item/3640.aspx

朱卫国教授：https://med.szu.edu.cn/Item/322.aspx

 全文链接：https://link.springer.com/article/10.1007/s42764-022-00063-4

4.Ubiquitin carboxyl-terminal hydrolase 11 promotes autophagy by de-ubiquitinating and stabilizing Beclin-1 |Zheng Li, Shaohong Rao, Chunwei Song, Min Zhu, Hongchang Zhao, Shuping Yuan, Bin Peng & Xingzhi Xu

Beclin-1 is an important regulatory protein for autophagosome initiation and maturation. Here, Prof. Xingzhi Xu and his research team at Shenzhen University show that ubiquitin carboxy-terminal hydrolase 11 (USP11) deubiquitinates and stabilizes Beclin-1 both in vivo and in vitro, which in turn promotes autophagy. This finding reveals the regulatory role of USP11 on autophagy and suggests that Beclin-1 may be a therapeutic target for autophagy-related diseases.

    Beclin-1是自噬体启动和成熟的重要调控蛋白，深圳大学的许兴智教授团队报道了泛素羧基末端水解酶11（USP11）在体内外均能去泛素化并稳定Beclin-1，进而促进自噬。该发现揭示了USP11对自噬的调控作用，并提示Beclin-1可能是自噬相关疾病的治疗靶点。

许兴智教授: https://med.szu.edu.cn/Item/336.aspx

 全文链接：https://link.springer.com/article/10.1007/s42764-022-00061-6

  Volume 3 Issue 2

1. Target residence of Cas9: challenges and opportunities in genome editing | Yi-Li Feng, Meng Wang & An-Yong Xie

The clustered regularly interspaced palindromic repeats (CRISPR)/Cas9 system is a revolutionary gene editing technology that allows researchers to make changes quickly and easily to the genome. During this process of gene editing, Cas9 tightly binds to a cleaved target gene and protects DNA ends from the DNA damage response apparatus. In this review, An-Yong Xie and colleagues at Zhejiang University, China, explain how Cas9 regulates gene editing, focusing on how Cas9 residence on target genes affects DNA repair pathway choice in CRISPR/Cas9 genome editing. They also give their opinion on the challenges and opportunities faced by this application.

    CRISPR/Cas9是一项革命性的基因编辑技术，CRISPR核酸酶Cas9与靶向基因的结合与驻留时间的长短将影响到DNA损伤修复（DDR)过程。在这篇综述里，来自浙江大学的谢安勇团队向我们介绍了利用Cas9在靶向基因滞留的特点调控基因编辑，以及该应用面临的挑战和机遇。

冯依力博士：http://www.bio360.net/event/1?q=guest&gid=27

谢安勇教授：http://itm.zju.edu.cn/CN/lab.asp?t1=125&t2=180&t3=266

  全文链接：https://link.springer.com/article/10.1007/s42764-022-00066-1

2. Long non-coding RNAs regulate fatty acid and cholesterol metabolism| Kai Lei, Lei Qu, Fangzhou Liu, Ninghui Hao, Jincheng Chen, Jian Liu & Aifu Lin  

Long noncoding RNAs (IncRNAs) recently emerged as essential regulators of various physiological and pathological processes through their interactions with DNA, RNA and proteins. In this review, Dr. Jian Liu and Professor Aifu Lin at Zhejiang University, China, discuss the role IncRNAs play in lipid metabolism, specifically fatty acid and cholesterol biosynthesis, oxidation, and catabolism, as well as cholesterol efflux, influx and lipoprotein formation. They explain that by improving our understanding of the mechanisms and signaling pathways involving IncRNAs in lipid metabolism, we stand to open new avenues to prevent, diagnose and treat metabolic-related disorders.

    非编码长RNA (IncRNAs) 能够调节各种生理病理活动，在这篇综述里，来自浙江大学的刘坚研究员和林爱福教授团队向我们介绍了IncRNAs在脂肪酸和胆固醇生物合成、分解代谢和转移中的作用，帮助我们进一步了解lncRNAs在脂质代谢中的机制和相关的信号通路。

刘坚研究员：https://person.zju.edu.cn/liujian

林爱福教授 : https://person.zju.edu.cn/linlab

 全文链接：https://link.springer.com/article/10.1007/s42764-022-00070-5

3.Single-stranded RNA viruses activate and hijack host apical DNA damage response kinases for efficient viral replication| Pengcheng Li, Chenchen Xu, Xiaoyan Zhang, Cheng Cao, Xuejuan Wang & Gang Cai

ATM and ATR are two important kinases that regulate the DNA damage response (DDR). Here, Gang Cai and colleagues at the University of Science and Technology of China report that a single stranded RNA virus replication can activate the ATM and ATR pathway in host cells. Once activated, the ATM/ATR pathway promotes the expression of genes encoded by the viral genome and ultimately, viral replication. This finding reveals a new function of ATM/ATR beyond its role in regulating the DDR and provides a new research opening in the field of virus therapy.

    ATM和ATR是已知的调控DNA损伤反应（DDR)的两个重要激酶。来自中国科学技术大学的蔡刚团队报道了单链RNA病毒能够特异性诱导并激活宿主细胞中的ATM和ATR通路，激活的ATM/ATR反过来促进病毒基因的表达和复制。该发现揭示了ATM/ATR在调控DDR之外的功能,也为病毒治疗提供新的参考。

王雪娟教授及蔡刚教授：http://cailab.ustc.edu.cn/syscy/list.htm

 全文链接：https://link.springer.com/article/10.1007/s42764-022-00064-3

4.Proteome profiling of phosphatidylinositol-5-phosphate 4-kinase type 2A and 2B knockdown cells identify modifications in key regulators involved in cell homeostasis and genome integrity |Poorwa Awasthi, Ankur Kumar Srivastava, Vipin Kumar Yadav, Radhika Singh, Smriti Singh Yadav, Gururaj Rao Kidiyoor & Amit Kumar

Pip4k is a lipid kinase that helps to regulate various cellular processes; it is also often overexpressed in cancer. Here, Amit Kumar and colleagues at the CSIR Institute of Microbial Technology, India analyzed the effects of depleting one or both of the PIP4K isoforms (PIP4KA and PIP4KB) on various metabolic pathways and genomic stability. They found that PIP4K2A depletion perturbed ribosome assembly, translation, and cell proliferation while PIP4KB depletion affected apoptosis, DNA repair, and cell division. Co-depletion disrupted vesicle transport, cell motility, RNA splicing, and cell division, as well as the post-translational modifications (phosphorylation, acetylation) of proteins involved in nucleosome organization, mRNA splicing, and DNA replication. Interestingly, they found that cells harboring specific K-Ras mutations also overexpressed PIP4K2A and PIP4K2B. These data suggest that these enzymes might become new targets in particular cancer treatments.

    PIP4K是参与调控多个细胞过程的一种脂类激酶，在癌症中往往过度表达。来自印度CSIR微生物技术研究所的Amit Kumar和他的同事研究分析了PIP4K亚型的单一或共同缺失对各种代谢途径及基因组稳定性的影响，提示这些酶有可能成为治疗癌症的新靶点。

Amit Kumar: https://www.ceeri.res.in/profiles/amit-kumar/

  全文链接：https://link.springer.com/article/10.1007/s42764-022-00060-7

5. Differential molecular alterations promoting non-small cell lung cancer under hypoxia |Lina M. Al-Najjar, Malek Zihlif & Yazun Jarrar

Hypoxia is an important factor that can affect the tumor microenvironment. Here, Yazun Jarrar and colleagues from the University of Jordan showed that hypoxia promotes the over-expression of p53 in A549 lung cancer cells, which ultimately affects the cell cycle and the endothelial-mesenchymal transition. The result of this process is chemotherapy resistance and increased invasiveness of tumor cells. This finding helps explain why many patients with non-small cell lung cancer exhibit drug resistance and informs on alternative treatment options for those affected.

    缺氧是影响肿瘤微环境的重要因素之一。来自约旦大学的Yazun Jarrar及其同事报道了缺氧条件引起A549肺癌细胞p53的高表达，进而影响细胞周期和EMT，导致肿瘤细胞具有更强的化疗抵抗力和侵袭性。该发现为非小细胞肺癌的耐药性及其治疗提供了参考。

Yazun Jarrar : https://livedna.net/profile.php?dna=962.24115

全文链接：https://link.springer.com/article/10.1007/s42764-022-00062-5