Linked Life Data

15197179

Source:http://linkedlifedata.com/resource/pubmed/id/15197179

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
32
pubmed:dateCreated
2004-8-2
pubmed:abstractText
Replication protein A (RPA) is a heterotrimeric, single-stranded DNA-binding complex comprised of 70-kDa (RPA1), 32-kDa (RPA2), and 14-kDa (RPA3) subunits that is essential for DNA replication, recombination, and repair in eukaryotes. In addition, recent studies using vertebrate model systems have suggested an important role for RPA in the initiation of cell cycle checkpoints following exposure to DNA replication stress. Specifically, RPA has been implicated in the recruitment and activation of the ATM-Rad3-related protein kinase, ATR, which in conjunction with the related kinase, ATM (ataxia-telangiectasia-mutated), transmits checkpoint signals via the phosphorylation of downstream effectors. In this report, we have explored the effects of RPA insufficiency on DNA replication, cell survival, and ATM/ATR-dependent signal transduction in response to genotoxic stress. RNA interference-mediated suppression of RPA1 caused a slowing of S phase progression, G2/M cell cycle arrest, and apoptosis in HeLa cells. RPA-deficient cells demonstrated high levels of spontaneous DNA damage and constitutive activation of ATM, which was responsible for the terminal G2/M arrest phenotype. Surprisingly, we found that neither RPA1 nor RPA2 were essential for the hydroxyurea- or UV-induced phosphorylation of the ATR substrates CHK1 and CREB (cyclic AMP-response element-binding protein). These findings reveal that RPA is required for genomic stability and suggest that activation of ATR can occur through RPA-independent pathways.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
6
pubmed:volume
279
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
34010-4
pubmed:dateRevised
2011-11-2
pubmed:meshHeading
pubmed-meshheading:15197179-Cell Cycle, pubmed-meshheading:15197179-Cell Cycle Proteins, pubmed-meshheading:15197179-Cell Line, pubmed-meshheading:15197179-DNA Damage, pubmed-meshheading:15197179-DNA Replication, pubmed-meshheading:15197179-DNA-Binding Proteins, pubmed-meshheading:15197179-G2 Phase, pubmed-meshheading:15197179-Gene Expression, pubmed-meshheading:15197179-HeLa Cells, pubmed-meshheading:15197179-Humans, pubmed-meshheading:15197179-Microscopy, Fluorescence, pubmed-meshheading:15197179-Mitosis, pubmed-meshheading:15197179-Phosphorylation, pubmed-meshheading:15197179-Protein-Serine-Threonine Kinases, pubmed-meshheading:15197179-RNA, Small Interfering, pubmed-meshheading:15197179-Replication Protein A, pubmed-meshheading:15197179-Serine, pubmed-meshheading:15197179-Transfection, pubmed-meshheading:15197179-Tumor Suppressor Proteins
pubmed:year
2004
pubmed:articleTitle
DNA replication defects, spontaneous DNA damage, and ATM-dependent checkpoint activation in replication protein A-deficient cells.
pubmed:affiliation
Department of Pharmacology, University of Wisconsin, Madison, Wisconsin 53706, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't