The tumour-suppressive roles of BRCA1 and 2 have been attributed to three seemingly distinct functions - homologous recombination, replication fork protection, and single-stranded (ss)DNA gap suppression - and their relative importance is under debate. In this review, we examine the origin and resolution of ssDNA gaps and discuss the recent advances in understanding the role of BRCA1/2 in gap suppression. There are ample data showing that gap accumulation in BRCA1/2-deficient cells is linked to genomic instability and chemosensitivity. However, it remains unclear whether there is a causative role and the function of BRCA1/2 in gap suppression cannot unambiguously be dissected from their other functions. We therefore conclude that the three functions of BRCA1 and 2 are closely intertwined and not mutually exclusive.
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| http://dx.doi.org/10.1016/j.tig.2024.04.013 | DOI Listing |
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