Cells deficient in PARP-1 show an accelerated accumulation of DNA single strand breaks, but not AP sites, over the PARP-1-proficient cells exposed to MMS.
Cells deficient in PARP-1 show an accelerated accumulation of DNA single strand breaks, but not AP sites, over the PARP-1-proficient cells exposed to MMS.
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DOI：
10.1016/j.mrfmmm.2009.09.006
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发表时间：
2009-12-01
影响因子：
2.3
通讯作者：
Nakamura, Jun
中科院分区：
文献类型：
--
作者：
Pachkowski, Brian F.;Tano, Keizo;Afonin, Valeriy;Elder, Rhoderick H.;Takeda, Shunichi;Watanabe, Masami;Swenberg, James A.;Nakamura, Jun
Poly(ADP-ribose) polymerase-1 (PARP-1) is a base excision repair (BER) protein that binds to DNA single strand breaks (SSBs) and subsequently synthesizes and transfers poly(ADP-ribose) polymers to various nuclear proteins. Numerous biochemical studies have implicated PARP-1 as a modulator of BER; however, the role of PARP-1 in BER in living cells remains unclear partly due to lack of accurate quantitation of BER intermediates existing in cells. Since DT40 cells, chicken B lymphocytes, naturally lack PARP-2, DT40 cells allow for the investigation of the PARP-1 null phenotype without confounding by PARP-2. To test the hypothesis that PARP-1 is necessary for efficient BER during methylmethane sulfonate (MMS) exposure in vertebrate cells, intact DT40 cells and their isogenic PARP-1 null counterparts were challenged with different exposure scenarios for phenotypic characterization. With chronic exposure, PARP-1 null cells exhibited sensitivity to MMS but with an acute exposure did not accumulate base lesions or AP sites to a greater extent than wild-type cells. However, an increase in SSB content in PARP-1 null cell DNA, as indicated by glyoxal gel electrophoresis under neutral conditions, suggested the presence of BER intermediates. These data suggest that during exposure, PARP-1 impacts the stage of BER after excision of the deoxyribosephosphate moiety from the 5’ end of DNA strand breaks by polymerase β.
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DOI：
10.1016/j.mrgentox.2009.05.006
发表时间：
2009-08
影响因子：
1.9
作者：
Boysen, Gunnar;Pachkowski, Brian F.;Nakamura, Jun;Swenberg, James A.
通讯作者：
Swenberg, James A.
影响因子：
11.4
作者：
Kubota, Y;Nash, RA;Lindahl, T
通讯作者：
Lindahl, T
通过PARP-1，需要通过PARP-1进行反馈调节的聚（ADP-核糖基），才能快速响应活细胞中的DNA损伤。
影响因子：
14.9
作者：
Mortusewicz, Oliver;Ame, Jean-Christophe;Schreiber, Valerie;Leonhardt, Heinrich
通讯作者：
Leonhardt, Heinrich
影响因子：
4.8
作者：
Nakamura, J;La, DK;Swenberg, JA
通讯作者：
Swenberg, JA
影响因子：
5.3
作者：
Fisher, Anna E. O.;Hochegger, Helfrid;Caldecott, Keith W.
通讯作者：
Caldecott, Keith W.