Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
37
pubmed:dateCreated
1995-10-12
pubmed:abstractText
p21, a p53-induced gene product that blocks cell cycle progression at the G1 phase, interacts with both cyclin-dependent kinases and proliferating cell nuclear antigen (PCNA). PCNA functions as a processivity factor for DNA polymerases delta and epsilon and is required for both DNA replication and nucleotide excision repair. Previous studies have shown that p21 inhibits simian virus 40 (SV40) DNA replication in HeLa cell extracts by interacting with PCNA. In this report we show that p21 blocks nucleotide excision repair of DNA that has been damaged by either ultraviolet radiation or alkylating agents, and that this inhibition can be reversed following addition of PCNA. We have determined that p21 is more effective in blocking DNA resynthesis than in inhibiting the excision step. We further show that a peptide derived from the carboxyl terminus of p21, which specifically interacts with PCNA, inhibits polymerase delta-catalyzed elongation of DNA chains almost stoichiometrically relative to the concentration of PCNA. When added at higher levels, this peptide also blocks both SV40 DNA replication and nucleotide excision repair in HeLa cell extracts. These results indicate that p21 interferes with the function of PCNA in both in vitro DNA replication and nucleotide excision repair.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
270
pubmed:geneSymbol
p53
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
22008-16
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:7665622-Amino Acid Sequence, pubmed-meshheading:7665622-Cell Cycle, pubmed-meshheading:7665622-Cyclin-Dependent Kinase Inhibitor p21, pubmed-meshheading:7665622-Cyclins, pubmed-meshheading:7665622-DNA Damage, pubmed-meshheading:7665622-DNA Repair, pubmed-meshheading:7665622-DNA Replication, pubmed-meshheading:7665622-Genes, p53, pubmed-meshheading:7665622-HeLa Cells, pubmed-meshheading:7665622-Histidine, pubmed-meshheading:7665622-Humans, pubmed-meshheading:7665622-Kinetics, pubmed-meshheading:7665622-Molecular Sequence Data, pubmed-meshheading:7665622-Peptide Fragments, pubmed-meshheading:7665622-Peptides, pubmed-meshheading:7665622-Proliferating Cell Nuclear Antigen, pubmed-meshheading:7665622-Sequence Tagged Sites, pubmed-meshheading:7665622-Simian virus 40, pubmed-meshheading:7665622-Ultraviolet Rays
pubmed:year
1995
pubmed:articleTitle
Inhibition of nucleotide excision repair by the cyclin-dependent kinase inhibitor p21.
pubmed:affiliation
Graduate Program in Molecular Biology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't