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

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 p...

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Autores principales: Dheekollu, Jayaraju, Deng, Zhong, Wiedmer, Andreas, Weitzman, Matthew D., Lieberman, Paul M.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2094660/
https://www.ncbi.nlm.nih.gov/pubmed/18040525
http://dx.doi.org/10.1371/journal.pone.0001257
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author Dheekollu, Jayaraju
Deng, Zhong
Wiedmer, Andreas
Weitzman, Matthew D.
Lieberman, Paul M.
author_facet Dheekollu, Jayaraju
Deng, Zhong
Wiedmer, Andreas
Weitzman, Matthew D.
Lieberman, Paul M.
author_sort Dheekollu, Jayaraju
collection PubMed
description 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.
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spelling pubmed-20946602007-12-05 A Role for MRE11, NBS1, and Recombination Junctions in Replication and Stable Maintenance of EBV Episomes Dheekollu, Jayaraju Deng, Zhong Wiedmer, Andreas Weitzman, Matthew D. Lieberman, Paul M. PLoS One Research Article 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. Public Library of Science 2007-12-05 /pmc/articles/PMC2094660/ /pubmed/18040525 http://dx.doi.org/10.1371/journal.pone.0001257 Text en Dheekollu et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Dheekollu, Jayaraju
Deng, Zhong
Wiedmer, Andreas
Weitzman, Matthew D.
Lieberman, Paul M.
A Role for MRE11, NBS1, and Recombination Junctions in Replication and Stable Maintenance of EBV Episomes
title A Role for MRE11, NBS1, and Recombination Junctions in Replication and Stable Maintenance of EBV Episomes
title_full A Role for MRE11, NBS1, and Recombination Junctions in Replication and Stable Maintenance of EBV Episomes
title_fullStr A Role for MRE11, NBS1, and Recombination Junctions in Replication and Stable Maintenance of EBV Episomes
title_full_unstemmed A Role for MRE11, NBS1, and Recombination Junctions in Replication and Stable Maintenance of EBV Episomes
title_short A Role for MRE11, NBS1, and Recombination Junctions in Replication and Stable Maintenance of EBV Episomes
title_sort role for mre11, nbs1, and recombination junctions in replication and stable maintenance of ebv episomes
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2094660/
https://www.ncbi.nlm.nih.gov/pubmed/18040525
http://dx.doi.org/10.1371/journal.pone.0001257
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