The ORFIUS complex regulates ORC2 localization at replication origins.

ABSTRACT: High-grade serous ovarian cancer (HGSC) is a lethal malignancy with elevated replication stress (RS) levels and defective RS and RS-associated DNA damage responses. Here we demonstrate that the bromodomain-containing protein BRD1 is a RS suppressing protein that forms a replication origin regulatory complex with the histone acetyltransferase HBO1, the BRCA1 tumor suppressor, and BARD1, ORigin FIring Under Stress (ORFIUS). BRD1 and HBO1 promote eventual origin firing by supporting localization of the origin licensing protein ORC2 at origins. In the absence of BRD1 and/or HBO1, both origin firing and nuclei with ORC2 foci are reduced. BRCA1 regulates BRD1, HBO1, and ORC2 localization at replication origins. In the absence of BRCA1, both origin firing and nuclei with BRD1, HBO1, and ORC2 foci

SUBMITTER: Yang Z 

PROVIDER: S-EPMC10823580 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature