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...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2007-12-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2094660?pdf=render |
| _version_ | 1819207235552673792 |
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| author | Jayaraju Dheekollu Zhong Deng Andreas Wiedmer Matthew D Weitzman Paul M Lieberman |
| author_facet | Jayaraju Dheekollu Zhong Deng Andreas Wiedmer Matthew D Weitzman Paul M Lieberman |
| author_sort | Jayaraju Dheekollu |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-23T05:20:16Z |
| format | Article |
| id | doaj.art-6d714780ada142b291cc198a4657ef68 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-23T05:20:16Z |
| publishDate | 2007-12-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-6d714780ada142b291cc198a4657ef682022-12-21T17:58:44ZengPublic Library of Science (PLoS)PLoS ONE1932-62032007-12-01212e125710.1371/journal.pone.0001257A role for MRE11, NBS1, and recombination junctions in replication and stable maintenance of EBV episomes.Jayaraju DheekolluZhong DengAndreas WiedmerMatthew D WeitzmanPaul M LiebermanRecombination-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.http://europepmc.org/articles/PMC2094660?pdf=render |
| spellingShingle | Jayaraju Dheekollu Zhong Deng Andreas Wiedmer Matthew D Weitzman Paul M Lieberman A role for MRE11, NBS1, and recombination junctions in replication and stable maintenance of EBV episomes. PLoS ONE |
| 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 |
| url | http://europepmc.org/articles/PMC2094660?pdf=render |
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