Functional Analysis of Chk2-Kiaa0170 Interaction

Abstract

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 G2/M checkpoint. These results suggest that MDC1 is an important mediator of DNA damage response and a potential tumor suppressor.

Open PDF

Document Details

Document Type
Technical Report
Publication Date
Sep 01, 2004
Accession Number
ADA429482

Entities

People

  • Zhenkun Lou

Organizations

  • Mayo Clinic

Tags

DTIC Thesaurus Topics

  • Amino Acids
  • Apoptosis
  • Breast Cancer
  • Cell Line
  • Cell Physiological Processes
  • Cells
  • Chemical Synthesis
  • Chemistry
  • Functional Analysis
  • Fungi
  • Ionizing Radiation
  • Molecular Biology
  • Neoplasms
  • Protein-Protein Interactions
  • Proteins
  • Radiation
  • Tumor Cell Line

Fields of Study

  • Biology

Readers

  • Cellular and Molecular Pathways of Apoptosis.
  • International Relations and Conflict Resolution
  • Molecular and genetic basis of cancer.