BRCA1: a key player at multiple stages of homologous recombination in DNA double-strand break repair

Yidan Liu; Lin-Yu Lu

doi:10.1007/s42764-021-00042-1

Genome Instability & Disease ›› 2021, Vol. 2 ›› Issue (3) : 164 -174. DOI: 10.1007/s42764-021-00042-1

Review Article

BRCA1: a key player at multiple stages of homologous recombination in DNA double-strand break repair

Yidan Liu ¹^,^a
, Lin-Yu Lu ¹^,²^,³^,^b

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Abstract

As a key tumor suppressor in several cancers, BRCA1 is required for the maintenance of genomic stability. Extensive studies have revealed multiple functions of BRCA1 that contribute to its role in tumor suppression, but the most recognized one is DNA damage repair, especially DNA double-strand break (DSB) repair. Once recruited to DSB in S/G2 phase of the cell cycle, BRCA1 promotes DSB repair through homologous recombination (HR). Mechanistically, it is well known that BRCA1 is required for the efficient loading of RAD51 recombinase to DSB. Studies in the past decade reveal that BRCA1 also regulates DNA end resection to generate single-stranded DNA (ssDNA) required for RAD51 loading and promotes RAD51-mediated synaptic complex assembly. In this review, we will summarize the underlying mechanisms of the recruitment BRCA1 to DSB and BRCA1’s functions at multiple stages of HR in DSB repair. We will also discuss how HR defects caused by BRCA1 deficiency can be rescued by modulating DSB repair pathway choice.

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Yidan Liu, Lin-Yu Lu. BRCA1: a key player at multiple stages of homologous recombination in DNA double-strand break repair. Genome Instability & Disease, 2021, 2(3): 164-174 DOI:10.1007/s42764-021-00042-1