Mechanism of double-strand DNA break repair in heterochromatic region through liquid-liquid phase separation

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K22410
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 44:Biology at cellular to organismal levels, and related fields
• Research Institution: Tohoku University
• Principal Investigator: Tanaka Kozo 東北大学, 加齢医学研究所, 教授 (00304452)
• Project Period (FY): 2019-06-28 – 2021-03-31
• Keywords: 細胞・組織 / DNA損傷応答 / ヘテロクロマチン

Outline of Final Research Achievements

In this project, we aimed to elucidate how a novel protein CAMP contributes to liquid-liquid phase separation and DNA double-strand break repair. CAMP interacts with a heterochromatin factor HP1, which was reported to undergo liquid-liquid phase separation, and we found that CAMP itself forms droplet as well. The C-terminal region of CAMP was required for the droplet formation, and HP1 was included in the droplet formed by CAMP. On the other hand, CAMP plays a role in homologous recombinational repair of DNA double-strand breaks, and the C-terminal region of CAMP is required for the function. Collectively, it was suggested that CAMP is involved in both liquid-liquid phase separation and homologous recombination through its C-terminus.

Free Research Field

細胞生物学・分子腫瘍学

Academic Significance and Societal Importance of the Research Achievements

近年、液ー液相分離が様々な生命現象に関与することが急速に明らかになっている。本研究では、研究代表者が発見した新規分子CAMPに着目し、液ー液相分離とDNA損傷修復との関連について研究を行った。その結果、CAMPが細胞内の不活性化領域であるヘテロクロマチンの形成に関与するHP1と共に液滴を形成すること、CAMPのC末端領域が液滴形成と相同組換えによるDNA2本鎖切断修復の双方に関与することが明らかになった。最近HP1による液ー液相分離がヘテロクロマチン形成に関与することが報告されており、本研究の成果はヘテロクロマチン領域のDNA2本鎖切断にCAMPが関与する可能性を示すものである。