Elucidation of recognition and regulation of chromatin by innate immune DNA sensor cGAS

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K15711
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 43010:Molecular biology-related
• Research Institution: The University of Tokyo
• Principal Investigator: Kujirai Tomoya 東京大学, 定量生命科学研究所, 助教 (70823566)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: クロマチン / cGAS / ヌクレオソーム / 自然免疫

Outline of Final Research Achievements

Vertebrates have an innate immune DNA sensor cGAS to defend against foreign DNA such as viruses. On the other hand, cells have their own genomic DNA, and therefore cGAS must be inactivated against DNA that has formed chromatin. We have determined the three-dimensional structure of cGAS in complex with the nucleosome, the basic unit of chromatin, by cryo-EM analysis. Our results elucidate the mechanism of cGAS inactivation by nucleosomes.

Free Research Field

クロマチン

Academic Significance and Societal Importance of the Research Achievements

本研究で明らかになったcGASの制御機構は、自己と非自己のDNAの区別という、自然免疫分野における中心的な問に一つの答えを与えるものであると考えられる。また、cGASは、がん、老化、自己免疫疾患などの広範な疾病に関与している。本研究成果は、これらの疾病の発症のメカニズムや、制御法についての重要な知見を与えると期待される。