Functional Analysis of Chk2-Kiaa0170 Interaction
Abstract
We characterized one mechanism how BRCA1, a downstream effector of MDC1 and Chk2, in maintaining genomic stability. We show that BRCA1 interacts with topoisomerase II and regulates topoisomerase II activity and localization. In addition, we characterized the interaction between MDC1 and DNA-PKcs/Ku, an upstream regulator of Chk2. We show that MDC1 regulates DNA-PKcs phosphorylation and localization, and participates in DNA repair. Finally, we generated MDC1-/-mice and in the process of evaluating the physiological function of MDC1. Our preliminary data suggest that MDC1 plays an important role in DNA damage response and maintaining genomic stability. In summery, our studies revealed novel mechanisms of the DNA damage response pathway and our animal model of the MDC1 knockout mice will elucidate how dysfunction of the Chk2-MDC1 pathway contributes to the development of tumor.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2005
- Accession Number
- ADA449840
Entities
People
- Lou Zhenkun
Organizations
- Mayo Clinic