SPOP promotes transcriptional expression of DNA repair and replication factors to prevent replication stress and genomic instability.

ABSTRACT: Mutations in SPOP, the gene most frequently point-mutated in primary prostate cancer, are associated with a high degree of genomic instability and deficiency in homologous recombination repair of DNA but the underlying mechanisms behind this defect are currently unknown. Here we demonstrate that SPOP knockdown leads to spontaneous replication stress and impaired recovery from replication fork stalling. We show that this is associated with reduced expression of several key DNA repair and replication factors including BRCA2, ATR, CHK1 and RAD51. Consequently, SPOP knockdown impairs RAD51 foci formation and activation of CHK1 in response to replication stress and compromises recovery from replication fork stalling. An SPOP interactome analysis shows that wild type (WT) SPOP but not mutant SPO

SUBMITTER: Hjorth-Jensen K 

PROVIDER: S-EPMC6182143 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature