کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8324505 | 1539912 | 2012 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
BRCA1-dependent Chk1 phosphorylation triggers partial chromatin disassociation of phosphorylated Chk1 and facilitates S-phase cell cycle arrest
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کلمات کلیدی
PI3KFACSChk1ATReGFPRT-PCRataxia telangiectasia mutated - Ataxia telangiectasia جهش یافته استCell cycle checkpoint - ایست بازرسی چرخه سلولیionizing radiation - تابش یوننده یا پرتوهای یونیزانATM - خودپردازfluorescence-activated cell sorting - دسته بندی سلول های فعال فلورسنسcisplatin - سیس پلاتینPhosphoinositide 3-kinases - فسفوئینوزیتید 3-kinasesreverse transcription-PCR - معکوس رونویسی PCRHydroxyurea - هیدروکسی اورهenhanced green fluorescence protein - پروتئین فلورسانس سبز افزایش یافته استBRCA1 - ژن BRCA1
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله

چکیده انگلیسی
Chk1 phosphorylation by the PI3-like kinases ATR and ATM is critical for its activation and its role in prevention of premature mitotic entry in response to DNA damage or stalled replication. The breast and ovarian tumor suppressor, BRCA1, is among several checkpoint mediators that are required for Chk1 activation by ATM and ATR. Previously we showed that BRCA1 is necessary for Chk1 phosphorylation and activation following ionizing radiation. BRCA1 has been implicated in S-phase checkpoint control yet its mechanism of action is not well characterized. Here we report that BRCA1 is critical for Chk1 phosphorylation in response to inhibition of replication by either cisplatin or hydroxyurea. While Chk1 phosphorylation of S317 is fully dependent on BRCA1, additional proteins may mediate S345 phosphorylation at later time points. In addition, we show that a subset of phosphorylated Chk1 is released from the chromatin in a BRCA1-dependent manner which may lead to the phosphorylation of Chk1 substrate, Cdc25C, on S216 and to S-phase checkpoint activation. Inhibition of Chk1 kinase by UCN-01 or expression of Chk1 phosphorylation mutants in which the serine residues were substituted with alanine residues abrogates BRCA1-dependent cell cycle arrest in response replication inhibition. These data reveal that BRCA1 facilitates Chk1 phosphorylation and its partial chromatin dissociation following replication inhibition that is likely to be required for S-phase checkpoint signaling.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: The International Journal of Biochemistry & Cell Biology - Volume 44, Issue 11, November 2012, Pages 1761-1769
Journal: The International Journal of Biochemistry & Cell Biology - Volume 44, Issue 11, November 2012, Pages 1761-1769
نویسندگان
Ronit I. Yarden, Sally Metsuyanim, Itay Pickholtz, Shabana Shabbeer, Hadass Tellio, Moshe Z. Papa,