کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1919556 1535662 2008 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Human XPF controls TRF2 and telomere length maintenance through distinctive mechanisms
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی سالمندی
پیش نمایش صفحه اول مقاله
Human XPF controls TRF2 and telomere length maintenance through distinctive mechanisms
چکیده انگلیسی

XPF–ERCC1, a structure-specific endonuclease, is involved in nucleotide excision repair, crosslink repair and homologous recombination. XPF–ERCC1 is also found to interact with TRF2, a duplex telomeric DNA binding protein. We have previously shown that XPF–ERCC1 is required for TRF2-promoted telomere shortening. However, whether XPF–ERCC1 by itself has a role in telomere length maintenance has not been determined. Here we report that overexpression of XPF induces telomere shortening in XPF-proficient cells whereas XPF complementation suppresses telomere lengthening in XPF-deficient cells. These results suggest that XPF–ERCC1 can function as a negative mediator of telomere length maintenance. In addition, we find that introduction of wild type XPF into XPF-deficient cells leads to over 40% reduction in TRF2 association with telomeric DNA, indicating that XPF–ERCC1 negatively regulates TRF2 binding to telomeric DNA. Furthermore, we show that XPF carrying mutations in the conserved nuclease domain fails to control TRF2 association with telomeric DNA but it is competent for modulating telomere length maintenance. These results imply that XPF–ERCC1 controls TRF2 and telomere length maintenance through two distinctive mechanisms, with the former requiring its nuclease activity. Our results further imply that TRF2 association with telomeres may be deregulated in cells derived from XPF patients.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Mechanisms of Ageing and Development - Volume 129, Issue 10, October 2008, Pages 602–610
نویسندگان
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