کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1997026 1065534 2009 13 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Cdk1 Participates in BRCA1-Dependent S Phase Checkpoint Control in Response to DNA Damage
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Cdk1 Participates in BRCA1-Dependent S Phase Checkpoint Control in Response to DNA Damage
چکیده انگلیسی

SummaryCdk2 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.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 35, Issue 3, 14 August 2009, Pages 327–339
نویسندگان
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