Hedglin Mark, Pandey Binod, Benkovic Stephen J
Department of Chemistry, The Pennsylvania State University, University Park, United States.
Elife. 2016 Oct 22;5:e19788. doi: 10.7554/eLife.19788.
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 η to sites of DNA damage where they may also displace a blocked replicative polymerase. We provide extensive quantitative evidence that the binding of pol η to PCNA and the ensuing TLS are both independent of PCNA ubiquitination. Rather, the unique properties of pols η and δ are attuned to promote an efficient and passive exchange of polymerases during TLS on the lagging strand.
S期的跨损伤DNA合成（TLS）利用特殊的TLS DNA聚合酶复制DNA损伤，使严格的DNA合成能够在有害损伤之外恢复。人类的TLS涉及泛素与环绕受损DNA的PCNA钳的结合，这种翻译后修饰的作用正在研究中。一个被广泛接受的模型认为，泛素化的PCNA将TLS聚合酶（如聚合酶η）招募到DNA损伤位点，在这些位点它们也可能取代受阻的复制性聚合酶。我们提供了大量定量证据，表明聚合酶η与PCNA的结合以及随后的TLS均独立于PCNA泛素化。相反，聚合酶η和δ的独特特性协调作用，以促进滞后链TLS过程中聚合酶的高效被动交换。
