An Aurora B-RPA signaling axis secures chromosome segregation fidelity

Poonam Roshan, Sahiti Kuppa, Jenna R. Mattice, Vikas Kaushik, Rahul Chadda, Nilisha Pokhrel, Brunda R. Tumala, Aparna Biswas, Brian Bothner, Edwin Antony () and Sofia Origanti ()
Additional contact information
Poonam Roshan: St. Louis University
Sahiti Kuppa: St. Louis University School of Medicine
Jenna R. Mattice: Montana State University
Vikas Kaushik: St. Louis University School of Medicine
Rahul Chadda: St. Louis University School of Medicine
Nilisha Pokhrel: Marquette University
Brunda R. Tumala: St. Louis University School of Medicine
Aparna Biswas: St. Louis University
Brian Bothner: Montana State University
Edwin Antony: St. Louis University School of Medicine
Sofia Origanti: St. Louis University

Nature Communications, 2023, vol. 14, issue 1, 1-19

Abstract: Abstract 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 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.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-023-38711-2 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38711-2

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-38711-2

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().