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. |