Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
24
pubmed:dateCreated
2008-11-25
pubmed:abstractText
ATR kinase activation requires the recruitment of the ATR-ATRIP and RAD9-HUS1-RAD1 (9-1-1) checkpoint complexes to sites of DNA damage or replication stress. Replication protein A (RPA) bound to single-stranded DNA is at least part of the molecular recognition element that recruits these checkpoint complexes. We have found that the basic cleft of the RPA70 N-terminal oligonucleotide-oligosaccharide fold (OB-fold) domain is a key determinant of checkpoint activation. This protein-protein interaction surface is able to bind several checkpoint proteins, including ATRIP, RAD9, and MRE11. RAD9 binding to RPA is mediated by an acidic peptide within the C-terminal RAD9 tail that has sequence similarity to the primary RPA-binding surface in the checkpoint recruitment domain (CRD) of ATRIP. Mutation of the RAD9 CRD impairs its localization to sites of DNA damage or replication stress without perturbing its ability to form the 9-1-1 complex or bind the ATR activator TopBP1. Disruption of the RAD9-RPA interaction also impairs ATR signaling to CHK1 and causes hypersensitivity to both DNA damage and replication stress. Thus, the basic cleft of the RPA70 N-terminal OB-fold domain binds multiple checkpoint proteins, including RAD9, to promote ATR signaling.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/18936170-10526407, http://linkedlifedata.com/resource/pubmed/commentcorrection/18936170-11000117, http://linkedlifedata.com/resource/pubmed/commentcorrection/18936170-11009611, http://linkedlifedata.com/resource/pubmed/commentcorrection/18936170-11721054, http://linkedlifedata.com/resource/pubmed/commentcorrection/18936170-12213834, http://linkedlifedata.com/resource/pubmed/commentcorrection/18936170-12535533, http://linkedlifedata.com/resource/pubmed/commentcorrection/18936170-12578958, http://linkedlifedata.com/resource/pubmed/commentcorrection/18936170-12734188, http://linkedlifedata.com/resource/pubmed/commentcorrection/18936170-12791985, http://linkedlifedata.com/resource/pubmed/commentcorrection/18936170-14605214, http://linkedlifedata.com/resource/pubmed/commentcorrection/18936170-14624239, http://linkedlifedata.com/resource/pubmed/commentcorrection/18936170-15090549, http://linkedlifedata.com/resource/pubmed/commentcorrection/18936170-15197179, http://linkedlifedata.com/resource/pubmed/commentcorrection/18936170-15282322, http://linkedlifedata.com/resource/pubmed/commentcorrection/18936170-15743907, http://linkedlifedata.com/resource/pubmed/commentcorrection/18936170-15829956, http://linkedlifedata.com/resource/pubmed/commentcorrection/18936170-15829965, http://linkedlifedata.com/resource/pubmed/commentcorrection/18936170-15833913, http://linkedlifedata.com/resource/pubmed/commentcorrection/18936170-15897895, http://linkedlifedata.com/resource/pubmed/commentcorrection/18936170-15964238, http://linkedlifedata.com/resource/pubmed/commentcorrection/18936170-16110319, http://linkedlifedata.com/resource/pubmed/commentcorrection/18936170-16186122, http://linkedlifedata.com/resource/pubmed/commentcorrection/18936170-16234232, http://linkedlifedata.com/resource/pubmed/commentcorrection/18936170-16327781, http://linkedlifedata.com/resource/pubmed/commentcorrection/18936170-16354678, http://linkedlifedata.com/resource/pubmed/commentcorrection/18936170-16407120, http://linkedlifedata.com/resource/pubmed/commentcorrection/18936170-16431910, http://linkedlifedata.com/resource/pubmed/commentcorrection/18936170-16461339, http://linkedlifedata.com/resource/pubmed/commentcorrection/18936170-16474843, http://linkedlifedata.com/resource/pubmed/commentcorrection/18936170-16530042, http://linkedlifedata.com/resource/pubmed/commentcorrection/18936170-16713580, http://linkedlifedata.com/resource/pubmed/commentcorrection/18936170-16753272, http://linkedlifedata.com/resource/pubmed/commentcorrection/18936170-16864589, http://linkedlifedata.com/resource/pubmed/commentcorrection/18936170-16935876, http://linkedlifedata.com/resource/pubmed/commentcorrection/18936170-16940174, http://linkedlifedata.com/resource/pubmed/commentcorrection/18936170-17339343, http://linkedlifedata.com/resource/pubmed/commentcorrection/18936170-17437996, http://linkedlifedata.com/resource/pubmed/commentcorrection/18936170-17531813, http://linkedlifedata.com/resource/pubmed/commentcorrection/18936170-17575048, http://linkedlifedata.com/resource/pubmed/commentcorrection/18936170-17591703, http://linkedlifedata.com/resource/pubmed/commentcorrection/18936170-17636252, http://linkedlifedata.com/resource/pubmed/commentcorrection/18936170-18406328, http://linkedlifedata.com/resource/pubmed/commentcorrection/18936170-18469000, http://linkedlifedata.com/resource/pubmed/commentcorrection/18936170-18519640, http://linkedlifedata.com/resource/pubmed/commentcorrection/18936170-18594563, http://linkedlifedata.com/resource/pubmed/commentcorrection/18936170-9539419, http://linkedlifedata.com/resource/pubmed/commentcorrection/18936170-9708741, http://linkedlifedata.com/resource/pubmed/commentcorrection/18936170-9716411
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1098-5549
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
28
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7345-53
pubmed:dateRevised
2010-12-3
pubmed:meshHeading
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