G6PC3 promotes genome maintenance and is a candidate mammary tumor suppressor.

ABSTRACT: Mutations in genome maintenance factors drive sporadic and hereditary breast cancers. Here, we searched for potential drivers based on germline DNA analysis from a cohort consisting of patients with early-onset breast cancer negative for BRCA1/BRCA2 mutations. This revealed candidate genes that subsequently were subjected to RNA interference-based (RNAi-based) phenotype screens to reveal genome integrity effects. We identified several genes with functional roles in genome maintenance, including Glucose-6-Phosphatase Catalytic Subunit 3 (G6PC3), SMC4, and CCDC108. Notably, G6PC3-deficient cells exhibited increased levels of γH2AX and micronuclei formation, along with defects in homologous recombination (HR) repair. Consistent with these observations, G6PC3 was required for the efficient rec

SUBMITTER: Li X 

PROVIDER: S-EPMC12220951 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature