Postreplicative mismatch repair factors are recruited to Epstein-Barr virus replication compartments
Postreplicative mismatch repair factors are recruited to Epstein-Barr virus replication compartments
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DOI：
10.1074/jbc.m510314200
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发表时间：
2006-04-21
影响因子：
4.8
通讯作者：
Tsurumi, T
中科院分区：
文献类型：
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作者：
Daikoku, T;Kudoh, A;Tsurumi, T
错配修复（MMR）系统在整个进化过程中高度保守，纠正细胞DNA复制过程中出现的核苷酸错配。我们在这里报道了增殖细胞核抗原（PCNA）、钳夹装载复合体（RF-C）和一系列MMR蛋白，如MSH-2、MSH-6、MLH1和hPSM2，可以组装到爱泼斯坦-巴尔病毒复制区室，即病毒DNA合成的位点。dna结合形式的PCNA水平随着病毒生产性复制的进展而增加。溴脱氧尿嘧啶标记的染色质免疫耗竭分析证实，在裂解复制过程中，PCNA被装载到新合成的病毒DNA以及BALF2和BMRF1病毒蛋白上。此外，抗pcna、- MSH2、- MSH3或- MSH6抗体可能通过病毒DNA基因组免疫沉淀BMRF1复制蛋白。PCNA装载可能触发一系列宿主MMR蛋白转移到病毒DNA合成位点。MMR因子可能用于修复病毒复制过程中出现的错配，或抑制中度分化（同源）序列之间的重组。
The mismatch repair (MMR) system, highly conserved throughout evolution, corrects nucleotide mispairing that arise during cellular DNA replication. We report here that proliferating cell nuclear antigen (PCNA), the clamp loader complex (RF-C), and a series of MMR proteins like MSH-2, MSH-6, MLH1, and hPSM2 can be assembled to Epstein-Barr virus replication compartments, the sites of viral DNA synthesis. Levels of the DNA-bound form of PCNA increased with progression of viral productive replication. Bromodeoxyuridine-labeled chromatin immunodepletion analyses confirmed that PCNA is loaded onto newly synthesized viral DNA as well as BALF2 and BMRF1 viral proteins during lytic replication. Furthermore, the anti-PCNA, - MSH2, - MSH3, or - MSH6 antibodies could immunoprecipitate BMRF1 replication protein probably via the viral DNA genome. PCNA loading might trigger transfer of a series of host MMR proteins to the sites of viral DNA synthesis. The MMR factors might function for the repair of mismatches that arise during viral replication or act to inhibit recombination between moderately divergent ( homologous) sequences.