Gen1,也称为Holliday junction resolvase,是一种重要的DNA修复酶,参与DNA双链断裂的修复过程。DNA双链断裂是细胞中最为严重的DNA损伤形式之一,如果不能及时修复,会导致基因组不稳定和细胞死亡。Gen1通过解离Holliday junctions,促进DNA双链断裂的修复,维持基因组的稳定性。
Gen1在多种生物学过程中发挥重要作用。首先,Gen1在早期肾脏发育中发挥关键作用。研究发现,Gen1突变会导致肾脏发育异常,如肾脏发育不全和输尿管重复等[4,5]。其次,Gen1在乳腺发育和肿瘤发生中也发挥重要作用。研究发现,Gen1突变与乳腺癌的发生和化疗敏感性有关[6,8]。此外,Gen1还在DNA损伤修复和细胞凋亡中发挥作用。研究发现,Gen1突变会导致DNA损伤修复能力下降和细胞凋亡异常[7,9]。
Gen1的突变与多种疾病的发生和发展密切相关。首先,Gen1突变与先天性肾脏和尿路异常(CAKUT)的发生有关。研究发现,Gen1突变会导致CAKUT的发生,如肾脏发育不全和输尿管重复等[1,2,4]。其次,Gen1突变与前列腺癌的发生和发展也有关。研究发现,Gen1突变与前列腺癌的侵袭性和转移性有关[3]。此外,Gen1突变还与乳腺癌的发生和发展有关[8]。
综上所述,Gen1是一种重要的DNA修复酶,参与DNA双链断裂的修复过程,维持基因组的稳定性。Gen1在早期肾脏发育、乳腺发育和肿瘤发生等多种生物学过程中发挥重要作用。Gen1的突变与多种疾病的发生和发展密切相关,包括CAKUT、前列腺癌和乳腺癌等。Gen1的研究有助于深入理解DNA修复的生物学功能和疾病发生机制,为疾病的治疗和预防提供新的思路和策略。
参考文献:
1. Du, Xuanjin, Wang, Chunyan, Liu, Jialu, Xu, Hong, Shen, Qian. 2024. GEN1 as a risk factor for human congenital anomalies of the kidney and urinary tract. In Human genomics, 18, 41. doi:10.1186/s40246-024-00606-8. https://pubmed.ncbi.nlm.nih.gov/38654324/
2. Zhang, Ya, Zhang, Xin, Wang, Xiaowen, Xu, Hong, Shen, Qian. 2019. Gen1 Modulates Metanephric Morphology Through Retinoic Acid Signaling. In DNA and cell biology, 38, 263-271. doi:10.1089/dna.2018.4426. https://pubmed.ncbi.nlm.nih.gov/30632787/
3. Darst, Burcu F, Saunders, Ed, Dadaev, Tokhir, Kote-Jarai, Zsofia, Haiman, Christopher A. . Germline Sequencing Analysis to Inform Clinical Gene Panel Testing for Aggressive Prostate Cancer. In JAMA oncology, 9, 1514-1524. doi:10.1001/jamaoncol.2023.3482. https://pubmed.ncbi.nlm.nih.gov/37733366/
4. Li, Yaxin, Yu, Minghui, Tan, Lihong, Xu, Hong, Shen, Qian. 2021. Disruption of Gen1 causes ectopic budding and kidney hypoplasia in mice. In Biochemical and biophysical research communications, 589, 173-179. doi:10.1016/j.bbrc.2021.11.041. https://pubmed.ncbi.nlm.nih.gov/34922199/
5. Wang, Xiaowen, Wang, Herui, Liu, Jiaojiao, Shen, Qian, Xu, Hong. 2020. Gen1 mutation caused kidney hypoplasia and defective ureter-bladder connections in mice. In International journal of biological sciences, 16, 1640-1647. doi:10.7150/ijbs.42855. https://pubmed.ncbi.nlm.nih.gov/32226308/
6. Sun, Lihua, Zhang, Yifang, Pan, Zhenxiang, Sun, Mei, Zhang, Xingyi. 2014. Expression and localization of GEN1 in mouse mammary epithelial cells. In Journal of biochemical and molecular toxicology, 28, 450-5. doi:10.1002/jbt.21584. https://pubmed.ncbi.nlm.nih.gov/24980922/
7. Svendsen, Jennifer M, Harper, J Wade. 2010. GEN1/Yen1 and the SLX4 complex: Solutions to the problem of Holliday junction resolution. In Genes & development, 24, 521-36. doi:10.1101/gad.1903510. https://pubmed.ncbi.nlm.nih.gov/20203129/
8. Turnbull, Clare, Hines, Sarah, Renwick, Anthony, Stratton, Michael R, Rahman, Nazneen. 2010. Mutation and association analysis of GEN1 in breast cancer susceptibility. In Breast cancer research and treatment, 124, 283-8. doi:10.1007/s10549-010-0949-1. https://pubmed.ncbi.nlm.nih.gov/20512659/
9. Wu, Yunlu, Qian, Ying, Zhou, Guozhong, Yan, Qiuyue, Dong, Xuejun. 2016. Effect of GEN1 interference on the chemosensitivity of the breast cancer MCF-7 and SKBR3 cell lines. In Oncology letters, 11, 3597-3604. doi:. https://pubmed.ncbi.nlm.nih.gov/27284361/