The BRCA1 coiled-coil domain is dispensable for suppression of tandem duplications and tolerance of FANCM loss

ABSTRACT: BRCA1-linked cancers contain abundant ~10 kb 'Group 1' tandem duplications (TDs). Group 1 TDs form at a Tus/Ter replication-fork barrier in DNA-end resection-defective mouse embryonic stem (mES) cells lacking Brca1 exon 11. To elucidate how BRCA1 suppresses Group 1 TDs, we analyzed Brca1 coiled-coil (CC)-domain mutants-separation-of-function alleles impaired for homologous recombination (HR) through loss of PALB2-binding and RAD51-loading functions but competent for DNA-end resection. Notably, Brca1 CC mutants retain the ability to suppress Group 1 TDs in the Tus/Ter system and in a mouse model of Brca1-linked mammary tumorigenesis. These data suggest that Brca1 CC domain-mutant cancers follow a path of tumorigenesis distinct from that of other Brca1-linked cancers. FANCM is a TD co-suppre

SUBMITTER: Namrata, M Nilavar 

PROVIDER: S-SCDT-10_1038-S44318-026-00913-X | biostudies-other |

REPOSITORIES: biostudies-other