DNA polymerase IV mediates efficient and quick recovery of replication forks stalled at N2-dG adducts.

DNA polymerase IV mediates efficient and quick recovery of replication forks stalled at N2-dG adducts.
复制标题

DNA 聚合酶 IV 介导在 N2-dG 加合物处停滞的复制叉的高效快速恢复。

DOI:
10.1093/nar/gku547
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发表时间:
2014-07
影响因子:
14.9
通讯作者:
Maki H
Maki H
中科院分区:
生物学2区
文献类型:
--
作者:
Ikeda M;Furukohri A;Philippin G;Loechler E;Akiyama MT;Katayama T;Fuchs RP;Maki H

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大肠杆菌DNA聚合酶IV(Escherichia coli DNA polymerase IV,Pol IV,也称为DinB)是一种Y家族DNA聚合酶,能够催化某些DNA损伤的跨损伤DNA合成(translesion DNA synthesis,TLS),大量数据表明Pol IV可能在复制包括N2-dG加合物和烷基化碱基在内的各种自发DNA损伤中发挥重要作用。Pol IV具有与Pol III在同一β钳上共存的独特能力,并以浓度依赖性方式使Pol III从β钳上正解离。用E. coli复制机制和Pol IV,我们观察到在前导链上的(-)-trans-anti-benzo[a]pyrene-N2-dG损伤处停滞的复制叉通过两个顺序的开关从Pol III到Pol IV和回到Pol III而有效且快速地恢复。我们的研究结果表明,TLS的Pol IV平滑的方式为复制叉以最小的中断。
Escherichia coli DNA polymerase IV (Pol IV, also known as DinB) is a Y-family DNA polymerase capable of catalyzing translesion DNA synthesis (TLS) on certain DNA lesions, and accumulating data suggest that Pol IV may play an important role in copying various kinds of spontaneous DNA damage including N2-dG adducts and alkylated bases. Pol IV has a unique ability to coexist with Pol III on the same β clamp and to positively dissociate Pol III from β clamp in a concentration-dependent manner. Reconstituting the entire process of TLS in vitro using E. coli replication machinery and Pol IV, we observed that a replication fork stalled at (−)-trans-anti-benzo[a]pyrene-N2-dG lesion on the leading strand was efficiently and quickly recovered via two sequential switches from Pol III to Pol IV and back to Pol III. Our results suggest that TLS by Pol IV smoothes the way for the replication fork with minimal interruption.
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