کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1981350 1061924 2007 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
ATR signaling mediates an S-phase checkpoint after inhibition of poly(ADP-ribose) polymerase activity
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
ATR signaling mediates an S-phase checkpoint after inhibition of poly(ADP-ribose) polymerase activity
چکیده انگلیسی

Human fibroblasts, capable of expressing a kinase-dead form of ATR (ATRkd), can be sensitized to the cytotoxic effects of methyl methanesulfonate (MMS) by the PARP inhibitor 4-amino-1,8-naphthalimide (4-AN). The combination of MMS + 4-AN results in accumulation of cells in S-phase of the cell cycle and activation of Chk1. Inhibition of ATR activity by expression of ATRkd suppresses the S-phase accumulation and partially reverses the Chk1 phosphorylation. The results confirm involvement of an ATR-mediated damage response pathway in the MMS + 4-AN-induced S-phase cell cycle checkpoint in human fibroblasts. Consistent with this hypothesis, the inhibitors caffeine and UCN-01 also abrogate the ATR- and Chk1-mediated delay in progression through S-phase. In the absence of ATR-mediated signaling, MMS + 4-AN exposure results in a G2/M arrest, rather than an S-phase checkpoint. Thus, whereas ATR mediates the S-phase response, it is not critical for arrest of cells in G2/M.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: DNA Repair - Volume 6, Issue 6, 1 June 2007, Pages 742–750
نویسندگان
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