Regulation of DNA repair machinery by K6- and K63-linked polyubiquitin chains

2016 Fiscal Year Final Research Report

• Project Area: New aspect of the ubiquitin system : its enormous roles in protein regulation
• Project/Area Number: 24112005
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: St. Marianna University School of Medicine
• Principal Investigator: OHTA Tomohiko 聖マリアンナ医科大学, 医学研究科, 教授 (60233136)
• Project Period (FY): 2012-06-28 – 2017-03-31
• Keywords: ユビキチン / BRCA1 / DNA修復 / 乳癌 / 薬剤感受性

Outline of Final Research Achievements

Retention of BRCA1 at sites of DNA damage through interaction with K63-linked polyubiquitin chains is important for homologous recombination repair of DNA breaks. In this study, we revealed that K-63 chains are rather required for non-homologous end-joining and the BRCA1 complex that executes the homologous recombination is retained at DSB sites through interaction of BARD1 with HP1γ, which subsequently interacts with Lys9-dimethylated histone H3 (H3K9me2) in an ATM-dependent manner. We also found a novel ligand-dependent non-genomic action of ER that stimulates the activity of UBE3C E3 ligase during mitosis and enhances cell proliferation. In addition we discovered a novel role of HERC2 E3 ligase activity on chromosome stability.

Free Research Field

癌化学療法感受性を左右するDNA損傷応答機構におけるユビキチン修飾の役割