Cdk1 participates in BRCA1-dependent S phase checkpoint control in response to DNA damage.
Data(s) |
14/08/2009
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Resumo |
Cdk2 and cdk1 are individually dispensable for cell-cycle progression in cancer cell lines because they are able to compensate for one another. However, shRNA-mediated depletion of cdk1 alone or small molecule cdk1 inhibition abrogated S phase cell-cycle arrest and the phosphorylation of a subset of ATR/ATM targets after DNA damage. Loss of DNA damage-induced checkpoint control was caused by a reduction in formation of BRCA1-containing foci. Mutation of BRCA1 at S1497 and S1189/S1191 resulted in loss of cdk1-mediated phosphorylation and also compromised formation of BRCA1-containing foci. Abrogation of checkpoint control after cdk1 depletion or inhibition in non-small-cell lung cancer cells sensitized them to DNA-damaging agents. Conversely, reduced cdk1 activity caused more potent G2/M arrest in nontransformed cells and antagonized the response to subsequent DNA damage. Cdk1 inhibition may therefore selectively sensitize BRCA1-proficient cancer cells to DNA-damaging treatments by disrupting BRCA1 function. |
Identificador | |
Idioma(s) |
eng |
Direitos |
info:eu-repo/semantics/restrictedAccess |
Fonte |
Johnson , N , Cal , D , Kennedy , R , Pathania , S , Arora , M , Li , Y , D\'Andrea , A D , Parvin , J D & Shapiro , G I 2009 , ' Cdk1 participates in BRCA1-dependent S phase checkpoint control in response to DNA damage. ' Molecular Cell , vol 35 , no. 3 , pp. 327-339 . DOI: 10.1016/j.molcel.2009.06.036 |
Palavras-Chave | #/dk/atira/pure/subjectarea/asjc/1300/1312 #Molecular Biology #/dk/atira/pure/subjectarea/asjc/1300/1307 #Cell Biology |
Tipo |
article |