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

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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.