کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5506498 | 1400297 | 2016 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Mdc1 modulates the interaction between TopBP1 and the MRN complex during DNA damage checkpoint responses
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کلمات کلیدی
ATM and Rad3-relateddouble-stranded DNA breakNBS1TopBP1mDC1Chk1ATRDSBataxia-telangiectasia mutated - Ataxia-Telangiectasia جهش یافته استSmall interfering RNA - RNA تداخل کوچکsiRNA - siRNAcheckpoint kinase 1 - بازرسی کیناز 1ionizing radiation - تابش یوننده یا پرتوهای یونیزانATM - خودپردازMRN complex - مجتمع MRNDNA damage checkpoint - نقطه بازرسی آسیب DNAmediator of DNA damage checkpoint protein 1 - واسطه ژن پروتئین پروتئین 1
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله

چکیده انگلیسی
TopBP1 has been identified as a direct activator of ATR and interacts with the Nbs1 subunit of the Mre11-Rad50-Nbs1 (MRN) complex in egg extracts in a checkpoint-regulated manner. In this study, we show that Mdc1 associates with both TopBP1 and Nbs1 in egg extracts and human cells. We cloned a cDNA encoding the full-length version of Xenopus Mdc1. The association between Mdc1 and TopBP1 involves the first pair of BRCT repeats in TopBP1. The N-terminal region (161-230) of Mdc1 is required for this binding. The interaction between Mdc1 and Nbs1 involves the two tandem BRCT repeats of Nbs1. Functional studies with mutated forms of Mdc1, TopBP1, and Nbs1 indicate that the BRCT-dependent association of these proteins is critical for a normal checkpoint response to DSBs. TopBP1 cannot interact with Nbs1 in Mdc1-depleted egg extracts, suggesting that Mdc1 connects TopBP1 and Nbs1 together. These findings suggest that Mdc1 is a crucial mediator of the DNA damage checkpoint response.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 479, Issue 1, 7 October 2016, Pages 5-11
Journal: Biochemical and Biophysical Research Communications - Volume 479, Issue 1, 7 October 2016, Pages 5-11
نویسندگان
Seung Ho Choi, Hae Yong Yoo,