Lau Patrick J, Kolodner Richard D
Ludwig Institute for Cancer Research, Cancer Center and Department of Medicine, University of California San Diego School of Medicine, La Jolla, California 92093-0660, USA.
J Biol Chem. 2003 Jan 3;278(1):14-7. doi: 10.1074/jbc.C200627200. Epub 2002 Nov 14.
Proliferating cell nuclear antigen (PCNA) is thought to play a role in DNA mismatch repair at the DNA synthesis step as well as in an earlier step. Studies showing that PCNA interacts with mispair-binding protein complexes, MSH2.MSH3 and MSH2.MSH6, and that PCNA enhances MSH2.MSH6 mispair binding specificity suggest PCNA may be involved in mispair recognition. Here we show that PCNA and MSH2.MSH6 form a stable ternary complex with a homoduplex (G/C) DNA, but MSH2.MSH6 binding to a heteroduplex (G/T) DNA disrupts MSH2.MSH6 binding to PCNA. We also found that the addition of ATP or adenosine 5'-O-(thiotriphosphate) restores MSH2.MSH6 binding to PCNA, presumably by disrupting MSH2.MSH6 binding to the heteroduplex (G/T) DNA. These results support a model in which MSH2.MSH6 binds to PCNA loaded on newly replicated DNA and is transferred from PCNA to mispaired bases in DNA.
增殖细胞核抗原（PCNA）被认为在DNA合成步骤以及更早的步骤中参与DNA错配修复。研究表明，PCNA与错配结合蛋白复合物MSH2.MSH3和MSH2.MSH6相互作用，并且PCNA增强MSH2.MSH6错配结合特异性，这表明PCNA可能参与错配识别。在此我们表明，PCNA和MSH2.MSH6与同型双链体（G/C）DNA形成稳定的三元复合物，但MSH2.MSH6与异型双链体（G/T）DNA的结合会破坏MSH2.MSH6与PCNA的结合。我们还发现，添加ATP或腺苷5'-O-（硫代三磷酸酯）可恢复MSH2.MSH6与PCNA的结合，推测是通过破坏MSH2.MSH6与异型双链体（G/T）DNA的结合。这些结果支持了一个模型，即MSH2.MSH6与加载在新复制DNA上的PCNA结合，并从PCNA转移到DNA中的错配碱基上。
