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dc.contributor.authorRoshan, Poonam
dc.contributor.authorKuppa, Sahiti
dc.contributor.authorMattice, Jenna R.
dc.contributor.authorKaushik, Vikas
dc.contributor.authorChadda, Rahul
dc.contributor.authorPokhrel, Nilisha
dc.contributor.authorTumala, Brunda R.
dc.contributor.authorBiswas, Aparna
dc.contributor.authorBothner, Brian
dc.contributor.authorAntony, Edwin
dc.contributor.authorOriganti, Sofia
dc.identifier.citationRoshan, P., Kuppa, S., Mattice, J.R. et al. An Aurora B-RPA signaling axis secures chromosome segregation fidelity. Nat Commun 14, 3008 (2023).
dc.description.abstractErrors 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 from RPA32. Disruption of Ser-384 phosphorylation in RPA70 leads to defects in chromosome segregation with loss of viability and a feedback modulation of Aurora B activity. Phosphorylation at Ser-384 remodels the protein interaction domains of RPA. Furthermore, phosphorylation impairs RPA binding to DSS1 that likely suppresses homologous recombination during mitosis by preventing recruitment of DSS1-BRCA2 to exposed ssDNA. We showcase a critical Aurora B-RPA signaling axis in mitosis that is essential for maintaining genomic integrity.en_US
dc.publisherSpringer Science and Business Media LLCen_US
dc.subjectchromosome segregationen_US
dc.subjectchromosome fidelityen_US
dc.titleAn Aurora B-RPA signaling axis secures chromosome segregation fidelityen_US
mus.citation.journaltitleNature Communicationsen_US
mus.relation.collegeCollege of Letters & Scienceen_US
mus.relation.departmentChemistry & Biochemistry.en_US
mus.relation.universityMontana State University - Bozemanen_US

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