Roles for the 8-Oxoguanine DNA Repair System in Protecting Telomeres From Oxidative Stress.
Roles for the 8-Oxoguanine DNA Repair System in Protecting Telomeres From Oxidative Stress.
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DOI：
10.3389/fcell.2021.758402
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发表时间：
2021
影响因子：
5.5
通讯作者：
Opresko PL
中科院分区：
文献类型：
--
作者：
De Rosa M;Johnson SA;Opresko PL
端粒是一种保护性的核蛋白结构，它覆盖在线性染色体末端，维护基因组的稳定性。在每次体细胞分裂时端粒逐渐缩短，最终会导致端粒过短且功能失调，这可能导致细胞衰老和老化，或者肿瘤发生。人类生殖细胞、一些干细胞以及大多数癌细胞会表达端粒酶来恢复端粒DNA。大量研究表明，由过量活性氧引起的氧化应激与端粒加速缩短和功能失调有关。端粒重复序列极易受到氧化损伤，并且是产生诱变性碱基损伤产物8 - 氧鸟嘌呤的首选位点，这会改变端粒长度的稳态和完整性。因此，了解端粒上8 - 氧鸟嘌呤处理所涉及的修复途径对于深入理解与端粒不稳定相关的退行性疾病和癌症的发病机制非常重要。高度保守的鸟嘌呤氧化（GO）系统涉及三种特殊的酶，它们启动不同的途径以专门减轻8 - 氧鸟嘌呤的不良影响。在此我们介绍GO系统，并综述那些专注于研究端粒上8 - 氧鸟嘌呤的处理如何影响端粒完整性和整体基因组稳定性的研究。我们还讨论了一些新开发的技术，这些技术选择性地针对端粒的氧化损伤，以研究GO系统在端粒稳定性中的作用。
Telomeres are protective nucleoprotein structures that cap linear chromosome ends and safeguard genome stability. Progressive telomere shortening at each somatic cell division eventually leads to critically short and dysfunctional telomeres, which can contribute to either cellular senescence and aging, or tumorigenesis. Human reproductive cells, some stem cells, and most cancer cells, express the enzyme telomerase to restore telomeric DNA. Numerous studies have shown that oxidative stress caused by excess reactive oxygen species is associated with accelerated telomere shortening and dysfunction. Telomeric repeat sequences are remarkably susceptible to oxidative damage and are preferred sites for the production of the mutagenic base lesion 8-oxoguanine, which can alter telomere length homeostasis and integrity. Therefore, knowledge of the repair pathways involved in the processing of 8-oxoguanine at telomeres is important for advancing understanding of the pathogenesis of degenerative diseases and cancer associated with telomere instability. The highly conserved guanine oxidation (GO) system involves three specialized enzymes that initiate distinct pathways to specifically mitigate the adverse effects of 8-oxoguanine. Here we introduce the GO system and review the studies focused on investigating how telomeric 8-oxoguanine processing affects telomere integrity and overall genome stability. We also discuss newly developed technologies that target oxidative damage selectively to telomeres to investigate roles for the GO system in telomere stability.
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影响因子：
10.5
作者：
Ahmed W;Lingner J
通讯作者：
Lingner J
DOI：
10.1073/pnas.0609410104
发表时间：
2007-02-13
影响因子：
11.1
作者：
Crabbe, Laure;Jauch, Anna;Karlseder, Jan
通讯作者：
Karlseder, Jan
DOI：
10.3390/life10110265
发表时间：
2020-10-31
期刊：
Life (Basel, Switzerland)
影响因子：
--
作者：
Garrido-Navas MC;Tippins F;Barwell J;Hoffman J;Codd V;Royle NJ
通讯作者：
Royle NJ
影响因子：
16.6
作者：
Croteau DL;Popuri V;Opresko PL;Bohr VA
通讯作者：
Bohr VA
影响因子：
4.6
作者：
Askeland G;Dosoudilova Z;Rodinova M;Klempir J;Liskova I;Kuśnierczyk A;Bjørås M;Nesse G;Klungland A;Hansikova H;Eide L
通讯作者：
Eide L