Regulation of Rad6/Rad18 Activity During DNA Damage Tolerance.

IF 10.4 1区生物学 Q1 BIOPHYSICS

Annual Review of Biophysics Pub Date : 2015-01-01 DOI:10.1146/annurev-biophys-060414-033841

Mark Hedglin, Stephen J Benkovic

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Abstract

Replicative polymerases (pols) cannot accommodate damaged template bases, and these pols stall when such offenses are encountered during S phase. Rather than repairing the damaged base, replication past it may proceed via one of two DNA damage tolerance (DDT) pathways, allowing replicative DNA synthesis to resume. In translesion DNA synthesis (TLS), a specialized TLS pol is recruited to catalyze stable, yet often erroneous, nucleotide incorporation opposite damaged template bases. In template switching, the newly synthesized sister strand is used as a damage-free template to synthesize past the lesion. In eukaryotes, both pathways are regulated by the conjugation of ubiquitin to the PCNA sliding clamp by distinct E2/E3 pairs. Whereas monoubiquitination by Rad6/Rad18 mediates TLS, extension of this ubiquitin to a polyubiquitin chain by Ubc13-Mms2/Rad5 routes DDT to the template switching pathway. In this review, we focus on the monoubiquitination of PCNA by Rad6/Rad18 and summarize the current knowledge of how this process is regulated.

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DNA 损伤耐受过程中 Rad6/Rad18 活性的调控

复制聚合酶（pols）无法容纳受损的模板碱基，因此在 S 期遇到这种情况时，这些聚合酶就会停滞。与其修复受损碱基，还不如通过两种 DNA 损伤耐受（DDT）途径之一进行复制，使复制 DNA 合成得以恢复。在转座子 DNA 合成（TLS）过程中，一种专门的 TLS pol 被招募来催化与受损模板碱基相对的稳定但往往错误的核苷酸结合。在模板转换过程中，新合成的姐妹链被用作无损模板，在病变处进行合成。在真核生物中，这两种途径都是通过不同的 E2/E3 对泛素与 PCNA 滑动钳的连接来调节的。Rad6/Rad18 的单泛素化介导了 TLS，而 Ubc13-Mms2/Rad5 将这种泛素延伸为多泛素链则将 DDT 引向模板转换途径。在这篇综述中，我们将重点讨论 Rad6/Rad18 对 PCNA 的单泛素化，并总结目前对这一过程如何调控的认识。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Annual Review of Biophysics 生物-生物物理

CiteScore

21.00

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0.00%

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期刊介绍： The Annual Review of Biophysics, in publication since 1972, covers significant developments in the field of biophysics, including macromolecular structure, function and dynamics, theoretical and computational biophysics, molecular biophysics of the cell, physical systems biology, membrane biophysics, biotechnology, nanotechnology, and emerging techniques.