TopBP1 functions with 53BP1 in the G1 DNA damage checkpoint |
| |
Authors: | Rachele Cescutti Simona Negrini Masaoki Kohzaki Thanos D Halazonetis |
| |
Institution: | 1Department of Molecular Biology, University of Geneva, Geneva, Switzerland;2Department of Biochemistry, University of Geneva, Geneva, Switzerland |
| |
Abstract: | TopBP1 is a checkpoint protein that colocalizes with ATR at sites of DNA replication stress. In this study, we show that TopBP1 also colocalizes with 53BP1 at sites of DNA double‐strand breaks (DSBs), but only in the G1‐phase of the cell cycle. Recruitment of TopBP1 to sites of DNA replication stress was dependent on BRCT domains 1–2 and 7–8, whereas recruitment to sites of DNA DSBs was dependent on BRCT domains 1–2 and 4–5. The BRCT domains 4–5 interacted with 53BP1 and recruitment of TopBP1 to sites of DNA DSBs in G1 was dependent on 53BP1. As TopBP1 contains a domain important for ATR activation, we examined whether it contributes to the G1 cell cycle checkpoint. By monitoring the entry of irradiated G1 cells into S‐phase, we observed a checkpoint defect after siRNA‐mediated depletion of TopBP1, 53BP1 or ATM. Thus, TopBP1 may mediate the checkpoint function of 53BP1 in G1. |
| |
Keywords: | 53BP1 DNA damage G1 checkpoint ionizing radiation TopBP1 |
|
|