کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1935775 1050674 2008 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The interplay between hMLH1 and hMRE11: Role in MMR and the effect of hMLH1 mutations
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
The interplay between hMLH1 and hMRE11: Role in MMR and the effect of hMLH1 mutations
چکیده انگلیسی
Our previous studies indicate that hMRE11 plays a role in MMR, and this function of hMRE11 is most likely mediated by the hMLH1-hMRE11 interaction. Here, we explored the functional implications of the hMLH1-hMRE11 interaction in MMR and the effects of hMLH1 mutations on their interaction. Our in vitro MMR assay demonstrated that the dominant-negative hMRE11452-634 mutant peptide (i.e., harboring only the hMLH1-interacting domain) imparted a significant reduction in both 3′ excision and 3′-directed MMR activities. Furthermore, the expression of hMRE11452-634, and to a lesser extent hMRE111-634 (ATLD1), impaired G2/M checkpoint control in response to MNU and cisplatin treatments, rendering cells resistant to killings by these two anticancer drugs. Analysis of 38 hMLH1 missense mutations showed that the majority of mutations caused significant (>50%) reductions in their interaction with hMRE11, suggesting a potential link between aberrant protein interaction and the pathogenic effects of hMLH1 variants.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 370, Issue 2, 30 May 2008, Pages 338-343
نویسندگان
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