Mismatch Repair proteins are recruited to replicating DNA through interaction with Proliferating Cell Nuclear Antigen (PCNA).
Mismatch Repair proteins are recruited to replicating DNA through interaction with Proliferating Cell Nuclear Antigen (PCNA).
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DOI：
10.1093/nar/gkm943
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发表时间：
2008-01
影响因子：
14.9
通讯作者：
Melendy T
中科院分区：
文献类型：
--
作者：
Masih PJ;Kunnev D;Melendy T
错配修复（MMR）与DNA复制密切相关;然而，除了复制滑动钳（PCNA）在各种MMR功能中的作用外，DNA复制与MMR之间的联系一直难以研究。在这里，我们使用一个体外DNA复制系统的基础上猿猴病毒40，调查MMR招聘复制DNA。DNA复制和MMR蛋白都以来源依赖的方式被招募来复制DNA。引物合成是必需的招募PCNA和MMR蛋白，但不是招募单链DNA结合蛋白（RPA）。用基于p21的多肽阻断PCNA募集到复制DNA阻断PCNA和MMR，但不阻断RPA募集。一旦PCNA和随后复制所需的蛋白质被加载到DNA上，p21的加入使PCNA留在复制的DNA上，但主动取代MMR蛋白。这些研究结果表明，MMR机制被招募到复制DNA通过其与PCNA的相互作用，并表明，这是通过结合的MMR蛋白质的多蛋白质相互作用的网站上的PCNA。这些研究表明，该系统的效用，进一步调查的DNA复制在MMR的作用。
Mismatch Repair (MMR) is closely linked to DNA replication; however, other than the role of the replicative sliding clamp (PCNA) in various MMR functions, the linkage between DNA replication and MMR has been difficult to investigate. Here we use an in vitro DNA replication system based on simian virus 40, to investigate MMR recruitment to replicating DNA. Both DNA replication and MMR proteins are recruited to replicating DNA in an origin-dependent fashion. Primer synthesis is required for recruitment of both PCNA and MMR proteins, but not for recruitment of the single-stranded DNA-binding protein (RPA). Blocking PCNA recruitment to replicating DNA with a p21-based polypeptide blocks PCNA and MMR, but not RPA recruitment. Once PCNA and subsequent proteins required for replication are loaded onto DNA, addition of p21 leaves PCNA on the replicating DNA, but actively displaces MMR proteins. These findings indicate that the MMR machinery is recruited to replicating DNA through its interaction with PCNA, and suggests that this occurs via binding of the MMR proteins to the multi-protein interaction sites on PCNA. These studies demonstrate the utility of this system for further investigation of the role of DNA replication in MMR.
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影响因子：
5.4
作者：
Chen, G;Stenlund, A
通讯作者：
Stenlund, A
影响因子：
13.8
作者：
KOLODNER, RD
通讯作者：
KOLODNER, RD
影响因子：
10.5
作者：
ALANI, E;CHI, NW;KOLODNER, R
通讯作者：
KOLODNER, R
影响因子：
5.3
作者：
FIEN, K;STILLMAN, B
通讯作者：
STILLMAN, B
影响因子：
13.8
作者：
Kelman, Z;Hurwitz, J
通讯作者：
Hurwitz, J