Late steps of allelic break-induced replication suppress tandem duplication associated with BRCA1 deficiency.

ABSTRACT: Microhomology-mediated tandem duplication (TD) is a distinct mutational signature in BRCA1-deficient tumors. While several mechanisms have been proposed for its generation, much understanding comes from repeat-based reporters, which may not represent the region of the human genome lacking neighboring repeats. To address this limitation, we developed a repeat-less TD reporter and a PCR-based endogenous site-specific TD assay to examine TDs induced by replication-coupled single-ended DNA double-strand breaks (seDSBs) in Brca1-deficient mouse embryonic stem cells. While TDs induced by seDSBs were detectable in wild-type cells, they were significantly elevated in Brca1-deficient cells, independent of classical non-homologous end joining. Some of these TDs arose from allelic DNA synthesis follo

SUBMITTER: Huang ZC 

PROVIDER: S-EPMC12309385 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature