Linked Life Data

15184880

Source:http://linkedlifedata.com/resource/pubmed/id/15184880

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
33
pubmed:dateCreated
2004-7-22
pubmed:abstractText
The checkpoint sliding-clamp complex, Rad9/Rad1/Hus1, plays a critical role during initiation of checkpoint signals in response to DNA damage and replication disruption. We investigated the impact of loss of Rad1 on checkpoint function and on DNA replication in mammalian cells. We show that RAD1 is an essential gene for sustained cell proliferation and that loss of Rad1 causes destabilization of Rad9 and Hus1 and consequently disintegration of the sliding-clamp complex. In Rad1-depleted cells, Atr-dependent Chk1 activation was impaired whereas Atm-mediated Chk2 activation was unaffected, suggesting that the sliding clamp is required primarily in Atr-dependent signal activation. Disruption of sliding-clamp function also caused a major defect in S-phase control. Rad1-depleted cells exhibited an RDS phenotype, indicating that damage-induced S-phase arrest was compromised by Rad1 loss. Furthermore, lack of Rad1 also affected the efficiency of replication recovery from DNA synthesis blockage, resulting in a prolonged S phase. These deficiencies may perpetually generate DNA strand breakage as we have found chromosomal abnormalities in Rad1-depleted cells. We conclude that the Rad9/Rad1/Hus1 complex is essential for Atr-dependent checkpoint signaling, which may play critical roles in the facilitation of DNA replication and in the maintenance of genomic integrity.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0950-9232
pubmed:author
pubmed:copyrightInfo
Copyright 2004 Nature Publishing Group
pubmed:issnType
Print
pubmed:day
22
pubmed:volume
23
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5586-93
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Disruption of the Rad9/Rad1/Hus1 (9-1-1) complex leads to checkpoint signaling and replication defects.
pubmed:affiliation
Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.