Functional Analysis of Chk2-Kiaa0170 Interaction
Annual summary rept. 15 Aug 2003-14 Aug 2004
MAYO CLINIC ROCHESTER MN
Pagination or Media Count:
We Investigated functional interaction of Chk2 and Kiaa0170 renamed as MDC1. We found that MDC1 interacts with Chk2 in a DNA-damage dependent manner and colocalizes with Chk2 at the sites of DNA damage. Furthermore, we found that the FHA domain of MDC1 and the phosphorylated Thr68 of Chk2 mediate the MDC1-Chk2 interaction. Using MDC1 small interference RNA siRNA to downregulate MDC1, we found that MDC1 is important for Chk2- dependent functions, such as intra-S phase checkpoint, p53 stabilization, and ionizing radiation-induced apoptosis. We also found that MDC1 regulates BRCA1 localization and phosphorylation following DNA damage. Downregulation of MDC1 resulted in defective G2M checkpoint. These results suggest that MDC1 is an important mediator of DNA damage response and a potential tumor suppressor.
- Medicine and Medical Research