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Publication : MDC1 collaborates with TopBP1 in DNA replication checkpoint control.

First Author  Wang J Year  2011
Journal  J Cell Biol Volume  193
Issue  2 Pages  267-73
PubMed ID  21482717 Mgi Jnum  J:171350
Mgi Id  MGI:4949779 Doi  10.1083/jcb.201010026
Citation  Wang J, et al. (2011) MDC1 collaborates with TopBP1 in DNA replication checkpoint control. J Cell Biol 193(2):267-73
abstractText  Human TopBP1 is a major player in the control of the DNA replication checkpoint. In this study, we identified MDC1, a key checkpoint protein involved in the cellular response to DNA double-strand breaks, as a TopBP1-associated protein. The specific TopBP1-MDC1 interaction is mediated by the fifth BRCT domain of TopBP1 and the Ser-Asp-Thr (SDT) repeats of MDC1. In addition, we demonstrated that TopBP1 accumulation at stalled replication forks is promoted by the H2AX/MDC1 signaling cascade. Moreover, MDC1 is important for ATR-dependent Chk1 activation in response to replication stress. Collectively, our data suggest that MDC1 facilitates several important steps in both cellular DNA damage response and the DNA replication checkpoint.
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