biostudies-literatureRoshan PU.S. Department of Health & Human Services | NIH | National Institute of General Medical SciencesU.S. Department of Health & Human Services | NIH | National Cancer InstituteNCI NIH HHSU.S. Department of Health & Human Services | NIH | NIH Office of the DirectorNIGMS NIH HHSNIH HHS3008https://www.ebi.ac.uk/biostudies/studies/S-EPMC10212944biostudies-literatureUnknown14(1)Errors in chromosome segregation underlie genomic instability associated with cancers. Resolution of replication and recombination intermediates and protection of vulnerable single-stranded DNA (ssDNA) intermediates during mitotic progression requires the ssDNA binding protein Replication Protein A (RPA). However, the mechanisms that regulate RPA specifically during unperturbed mitotic progression are poorly resolved. RPA is a heterotrimer composed of RPA70, RPA32 and RPA14 subunits and is predominantly regulated through hyperphosphorylation of RPA32 in response to DNA damage. Here, we have uncovered a mitosis-specific regulation of RPA by Aurora B kinase. Aurora B phosphorylates Ser-384 in the DNA binding domain B of the large RPA70 subunit and highlights a mode of regulation distinct froNature communicationsAn Aurora B-RPA signaling axis secures chromosome segregation fidelity.PMC10212944F99 CA274696R01 GM133967R01 GM130746OD28650S10 OD028650GM130746OD030343GM149320R35 GM149320GM143179S10 OD030343GM103474P30 CA091842CA274696GM133967P20 GM103474R01 GM143179Kuppa SKaushik VBothner BAntony EPokhrel NRoshan PChadda RBiswas AOriganti SMattice JRTumala BRfalseAn Aurora B-RPA signaling axis secures chromosome segregation fidelity.Errors in chromosome segregation underlie genomic instability associated with cancers. Resolution of replication and recombination intermediates and protection of vulnerable single-stranded DNA (ssDNA) intermediates during mitotic progression requires the ssDNA binding protein Replication Protein A (RPA). However, the mechanisms that regulate RPA specifically during unperturbed mitotic progression are poorly resolved. RPA is a heterotrimer composed of RPA70, RPA32 and RPA14 subunits and is predominantly regulated through hyperphosphorylation of RPA32 in response to DNA damage. Here, we have uncovered a mitosis-specific regulation of RPA by Aurora B kinase. Aurora B phosphorylates Ser-384 in the DNA binding domain B of the large RPA70 subunit and highlights a mode of regulation distinct fro2023-01-01T00:00:00Z2023 May2026-05-28T16:45:21.013Z2025-04-04T03:42:04.207ZS-EPMC102129443723096410.1038/s41467-023-38711-2