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rdf:type |
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lifeskim:mentions |
umls-concept:C0006812,
umls-concept:C0024660,
umls-concept:C0036667,
umls-concept:C0312418,
umls-concept:C0430054,
umls-concept:C0439855,
umls-concept:C1257825,
umls-concept:C1514873,
umls-concept:C1546857,
umls-concept:C1556066,
umls-concept:C1619636,
umls-concept:C1705053
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pubmed:issue |
4
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pubmed:dateCreated |
2010-11-24
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pubmed:abstractText |
Replication stress involving collision of replisomes with camptothecin (CPT)-stabilized DNA-Topoisomerase I adducts activates an ATR-dependent pathway to promote repair by homologous recombination. To identify human genes that protect cells from such replication stress, we performed a genome-wide CPT sensitivity screen. Among numerous candidate genes are two previously unstudied proteins: the ankyrin repeat protein NFKBIL2 and C6ORF167 (MMS22L), distantly related to yeast replication stress regulator Mms22p. MMS22L and NFKBIL2 interact with each other and with FACT (facilitator of chromatin transcription) and MCM (minichromosome maintenance) complexes. Cells depleted of NFKBIL2 or MMS22L are sensitive to DNA-damaging agents, load phosphorylated RPA onto chromatin in a CTIP-dependent manner, activate the ATR/ATRIP-CHK1 and double-strand break repair signaling pathways, and are defective in HR. This study identifies MMS22L-NFKBIL2 as components of the replication stress control pathway and provides a resource for discovery of additional components of this pathway.
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pubmed:grant |
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Camptothecin,
http://linkedlifedata.com/resource/pubmed/chemical/DNA synthesome,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Directed DNA Polymerase,
http://linkedlifedata.com/resource/pubmed/chemical/H2AFX protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Histones,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/MMS22L protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Multienzyme Complexes,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/RPA2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Replication Protein A,
http://linkedlifedata.com/resource/pubmed/chemical/TONSL protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/TP53BP1 protein, human
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
1097-4164
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pubmed:author |
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pubmed:copyrightInfo |
Copyright © 2010 Elsevier Inc. All rights reserved.
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pubmed:issnType |
Electronic
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pubmed:day |
24
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pubmed:volume |
40
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
645-57
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pubmed:dateRevised |
2011-10-6
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pubmed:meshHeading |
pubmed-meshheading:21055985-Camptothecin,
pubmed-meshheading:21055985-DNA Damage,
pubmed-meshheading:21055985-DNA Repair,
pubmed-meshheading:21055985-DNA Replication,
pubmed-meshheading:21055985-DNA-Binding Proteins,
pubmed-meshheading:21055985-DNA-Directed DNA Polymerase,
pubmed-meshheading:21055985-Drug Resistance, Neoplasm,
pubmed-meshheading:21055985-Genetic Testing,
pubmed-meshheading:21055985-Genome, Human,
pubmed-meshheading:21055985-Genomic Instability,
pubmed-meshheading:21055985-HeLa Cells,
pubmed-meshheading:21055985-Histones,
pubmed-meshheading:21055985-Humans,
pubmed-meshheading:21055985-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:21055985-Multienzyme Complexes,
pubmed-meshheading:21055985-NF-kappa B,
pubmed-meshheading:21055985-Nuclear Proteins,
pubmed-meshheading:21055985-Phosphorylation,
pubmed-meshheading:21055985-Protein Binding,
pubmed-meshheading:21055985-RNA, Small Interfering,
pubmed-meshheading:21055985-Recombination, Genetic,
pubmed-meshheading:21055985-Replication Protein A,
pubmed-meshheading:21055985-Reproducibility of Results,
pubmed-meshheading:21055985-Stress, Physiological
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pubmed:year |
2010
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pubmed:articleTitle |
A genome-wide camptothecin sensitivity screen identifies a mammalian MMS22L-NFKBIL2 complex required for genomic stability.
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pubmed:affiliation |
Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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