Adenovirus oncoproteins inactivate the Mre11-Rad50-NBS1 DNA repair complex

In mammalian cells, a conserved multiprotein complex of Mre11, Rad50 and NBS1 (also known as nibrin and p95) is important for double-strand break repair, meiotic recombination and telomere maintenance. This complex forms nuclear foci and may be a sensor of double-strand breaks. In the absence of the...

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Published in:Nature (London) 2002-07, Vol.418 (6895), p.348-352
Main Authors: Weitzman, Matthew D, Stracker, Travis H, Carson, Christian T
Format: Article
Language:English
Subjects:
Adenoviridae - genetics
Adenoviridae - metabolism
Adenoviridae - physiology
Adenovirus E1B Proteins - genetics
Adenovirus E1B Proteins - metabolism
Adenovirus E4 Proteins - genetics
Adenovirus E4 Proteins - metabolism
Biological and medical sciences
Cell Cycle Proteins - antagonists & inhibitors
Cell Cycle Proteins - chemistry
Cell Cycle Proteins - metabolism
Cell Line
Cell Transformation, Viral
Cellular biology
Deoxyribonucleic acid
DNA
DNA Damage
DNA Repair
DNA-Binding Proteins - antagonists & inhibitors
DNA-Binding Proteins - metabolism
Fluorescent Antibody Technique
Fundamental and applied biological sciences. Psychology
Fungal Proteins - antagonists & inhibitors
Fungal Proteins - metabolism
Genetics
HeLa Cells
Humans
Macromolecular Substances
Mammals
Microbiology
MRE11 Homologue Protein
Multiprotein Complexes
Nuclear Proteins - antagonists & inhibitors
Nuclear Proteins - chemistry
Nuclear Proteins - metabolism
Protein Binding
Proteins
Replicative cycle, interference, host-virus relations, pathogenicity, miscellaneous strains
Saccharomyces cerevisiae Proteins
Virology
Virus Replication
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container_issue 6895
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container_title Nature (London)
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creator Weitzman, Matthew D
Stracker, Travis H
Carson, Christian T
description In mammalian cells, a conserved multiprotein complex of Mre11, Rad50 and NBS1 (also known as nibrin and p95) is important for double-strand break repair, meiotic recombination and telomere maintenance. This complex forms nuclear foci and may be a sensor of double-strand breaks. In the absence of the early region E4, the double-stranded DNA genome of adenovirus is joined into concatemers too large to be packaged. We have investigated the cellular proteins involved in this concatemer formation and how they are inactivated by E4 products during a wild-type infection. Here we show that concatemerization requires functional Mre11 and NBS1, and that these proteins are found at foci adjacent to viral replication centres. Infection with wild-type virus results in both reorganization and degradation of members of the Mre11-Rad50-NBS1 complex. These activities are mediated by three viral oncoproteins that prevent concatemerization. This targeting of cellular proteins involved in genomic stability suggests a mechanism for 'hit-and-run' transformation observed for these viral oncoproteins.
doi_str_mv 10.1038/nature00863
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subjects Adenoviridae - genetics
Adenoviridae - metabolism
Adenoviridae - physiology
Adenovirus E1B Proteins - genetics
Adenovirus E1B Proteins - metabolism
Adenovirus E4 Proteins - genetics
Adenovirus E4 Proteins - metabolism
Biological and medical sciences
Cell Cycle Proteins - antagonists & inhibitors
Cell Cycle Proteins - chemistry
Cell Cycle Proteins - metabolism
Cell Line
Cell Transformation, Viral
Cellular biology
Deoxyribonucleic acid
DNA
DNA Damage
DNA Repair
DNA-Binding Proteins - antagonists & inhibitors
DNA-Binding Proteins - metabolism
Fluorescent Antibody Technique
Fundamental and applied biological sciences. Psychology
Fungal Proteins - antagonists & inhibitors
Fungal Proteins - metabolism
Genetics
HeLa Cells
Humans
Macromolecular Substances
Mammals
Microbiology
MRE11 Homologue Protein
Multiprotein Complexes
Nuclear Proteins - antagonists & inhibitors
Nuclear Proteins - chemistry
Nuclear Proteins - metabolism
Protein Binding
Proteins
Replicative cycle, interference, host-virus relations, pathogenicity, miscellaneous strains
Saccharomyces cerevisiae Proteins
Virology
Virus Replication
title Adenovirus oncoproteins inactivate the Mre11-Rad50-NBS1 DNA repair complex
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-01T09%3A54%3A00IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Adenovirus%20oncoproteins%20inactivate%20the%20Mre11-Rad50-NBS1%20DNA%20repair%20complex&rft.jtitle=Nature%20(London)&rft.au=Weitzman,%20Matthew%20D&rft.date=2002-07-18&rft.volume=418&rft.issue=6895&rft.spage=348&rft.epage=352&rft.pages=348-352&rft.issn=0028-0836&rft.eissn=1476-4687&rft.coden=NATUAS&rft_id=info:doi/10.1038/nature00863&rft_dat=%3Cgale_proqu%3EA187545928%3C/gale_proqu%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c605t-eac8b1b7341c81eb8fb57a53358d1d4926f4081007da25363735f455ac1a752b3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=204492571&rft_id=info:pmid/12124628&rft_galeid=A187545928&rfr_iscdi=true