Characterization of human translesion DNA synthesis across a UV-induced DNA lesion
Characterization of human translesion DNA synthesis across a UV-induced DNA lesion
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DOI：
10.7554/elife.19788
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发表时间：
2016-10-22
期刊：
影响因子：
7.7
通讯作者：
Benkovic, Stephen J.
中科院分区：
文献类型：
--
作者：
Hedglin, Mark;Pandey, Binod;Benkovic, Stephen J.
S期的translsion DNA合成（TLS）使用专门的TLS DNA聚合酶来复制DNA损伤，允许严格的DNA合成在损伤后恢复。人TLS涉及泛素与PCNA夹的缀合，所述PCNA夹环绕受损的DNA，并且这种翻译后修饰的作用正在审查中。一个被广泛接受的模型声称，泛素化的PCNA招募TLS聚合酶如pol eta到DNA损伤位点，在那里它们也可能取代被阻断的复制聚合酶。我们提供了大量的定量证据表明，pol eta与PCNA的结合和随后的TLS都独立于PCNA泛素化。相反，pols eta和delta的独特性质被调节以促进滞后链上的TLS期间聚合酶的有效和被动交换。
Translesion DNA synthesis (TLS) during S-phase uses specialized TLS DNA polymerases to replicate a DNA lesion, allowing stringent DNA synthesis to resume beyond the offending damage. Human TLS involves the conjugation of ubiquitin to PCNA clamps encircling damaged DNA and the role of this post-translational modification is under scrutiny. A widely accepted model purports that ubiquitinated PCNA recruits TLS polymerases such as pol eta to sites of DNA damage where they may also displace a blocked replicative polymerase. We provide extensive quantitative evidence that the binding of pol eta to PCNA and the ensuing TLS are both independent of PCNA ubiquitination. Rather, the unique properties of pols eta and delta are attuned to promote an efficient and passive exchange of polymerases during TLS on the lagging strand.