A Role for MRE11, NBS1, and Recombination Junctions in Replication and Stable Maintenance of EBV Episomes

被引：27

作者：

Dheekollu, Jayaraju ^{[1
]}

Deng, Zhong ^{[1
]}

Wiedmer, Andreas ^{[1
]}

Weitzman, Matthew D. ^{[2
]}

Lieberman, Paul M. ^{[1
]}

机构：

[1] Wistar Inst Anat & Biol, Philadelphia, PA USA

[2] Salk Inst Biol Studies, La Jolla, CA USA

来源：

PLOS ONE | 2007年 / 2卷 / 12期

关键词：

D O I：

10.1371/journal.pone.0001257

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Recombination-like structures formed at origins of DNA replication may contribute to replication fidelity, sister chromatid cohesion, chromosome segregation, and overall genome stability. The Epstein-Barr Virus (EBV) origin of plasmid replication ( OriP) provides episomal genome stability through a poorly understood mechanism. We show here that recombinational repair proteins MRE11 and NBS1 are recruited to the Dyad Symmetry (DS) region of OriP in a TRF2- and cell cycle-dependent manner. Depletion of MRE11 or NBS1 by siRNA inhibits OriP replication and destabilized viral episomes. OriP plasmid maintenance was defective in MRE11 and NBS1 hypomorphic fibroblast cell lines and only integrated, non-episomal forms of EBV were detected in a lympoblastoid cell line derived from an NBS1-mutated individual. Two-dimensional agarose gel analysis of OriP DNA revealed that recombination-like structures resembling Holliday-junctions form at OriP in mid S phase. MRE11 and NBS1 association with DS coincided with replication fork pausing and origin activation, which preceded the formation of recombination structures. We propose that NBS1 and MRE11 promote replication-associated recombination junctions essential for EBV episomal maintenance and genome stability.

引用

页数：12

共 73 条

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