2022 Fiscal Year Research-status Report

新規DNA相同組み換え機構に基づく細胞選択的合成致死誘導の開発

Research Project

Project/Area Number	20K08071
Research Institution	Yamagata University
Principal Investigator	田嶋克史山形大学, 医学部, 非常勤講師 (80292423)
Co-Investigator(Kenkyū-buntansha)	安田武嗣国立研究開発法人量子科学技術研究開発機構, 放射線医学総合研究所放射線障害治療研究部, 主幹研究員 (60332269)
Project Period (FY)	2020-04-01 – 2024-03-31
Keywords	RAD52 / DNA repair / double-strand break
Outline of Annual Research Achievements	Human RAD52 protein participates in single-strand annealing (SSA) and homologous recombinational (HR) repair at DNA double-strand break (DSB) sites, and it is also required for cell growth in BRCA2-deficient cells. Structural and biochemical analyses of RAD52 have identified several DNA-binding sites as lysine (K) and arginine (R) amino acid residues, in the groove of RAD52 ring. However, it is unclear which amino acids on RAD52 are involved in HR, SSA, and cell growth associated with BRCA2, respectively. Alanine (A) substitution of K and R revealed that K102, K152, and R153 DNA binding sites on RAD52 were essential for both SSA and HR, whereas K133 was only involved in SSA repair. K to alanine(A) substitution at 102 (K102A) deteriorated, not normal cell growth but only BRCA2-deficient cell growth. K133 might be involved in the pathway choice between HR and SSA repair. The present study provides insightful molecular properties for RDA52 functions and its applications.
Current Status of Research Progress	Current Status of Research Progress 3: Progress in research has been slightly delayed. Reason COVID-19流行の自然災害により施設間の研究交流ができなかったため
Strategy for Future Research Activity	COVID-19が2類から５類になり、施設間共同研究を円滑に行うことで研究計画を推進する。
Causes of Carryover	研究計画の自然災害（COVID-19）による遅延