Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2004-1-29
pubmed:abstractText
The breast cancer susceptibility protein, BRCA2, preserves chromosomal stability through roles in the repair of DNA double-strand breaks, and possibly, cell division. Post-translational modifications that may coordinate these functions remain poorly characterized. Here, we report that BRCA2 is a substrate for the mitotic Polo-like kinase, Plk1. BRCA2 undergoes phosphorylation in cells synchronously passing through the G2/M phases of cell cycle, when Plk1 expression and activity are maximal. Depletion of Plk1 by RNA interference suppresses BRCA2 modification. BRCA2 and Plk1 interact with one another in cell lysates, through a conserved region in BRCA2, which spans the eight BRC repeat motifs essential for its function in DNA repair. Within this region, residues positioned between BRC repeats--but not the repeat motifs themselves--are phosphorylated by Plk1. Interestingly, Plk1-mediated modification of BRCA2 during the G2/M phases is inhibited by treatment with the radiomimetic agent, adriamycin. Thus, our findings define a regulatory circuit for BRCA2 phosphorylation by Plk1 that is responsive to DNA damage as well as mitotic progression.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0950-9232
pubmed:author
pubmed:issnType
Print
pubmed:day
29
pubmed:volume
23
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
865-72
pubmed:dateRevised
2011-11-2
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Phosphorylation of BRCA2 by the Polo-like kinase Plk1 is regulated by DNA damage and mitotic progression.
pubmed:affiliation
CR UK Department of Oncology and the Medical Research Council Cancer Cell Unit, Hutchison/MRC Research Centre, University of Cambridge, Hills Road, Cambridge CB2 2XZ, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't