IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-38711-2.html
   My bibliography  Save this article

An Aurora B-RPA signaling axis secures chromosome segregation fidelity

Author

Listed:
  • 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)

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.

Suggested Citation

  • Poonam Roshan & Sahiti Kuppa & Jenna R. Mattice & Vikas Kaushik & Rahul Chadda & Nilisha Pokhrel & Brunda R. Tumala & Aparna Biswas & Brian Bothner & Edwin Antony & Sofia Origanti, 2023. "An Aurora B-RPA signaling axis secures chromosome segregation fidelity," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38711-2
    DOI: 10.1038/s41467-023-38711-2
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-38711-2
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-023-38711-2?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Manasvi Verma & Junhong Choi & Kyle A. Cottrell & Zeno Lavagnino & Erica N. Thomas & Slavica Pavlovic-Djuranovic & Pawel Szczesny & David W. Piston & Hani S. Zaher & Joseph D. Puglisi & Sergej Djurano, 2019. "A short translational ramp determines the efficiency of protein synthesis," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
    2. Ann-Marie K. Shorrocks & Samuel E. Jones & Kaima Tsukada & Carl A. Morrow & Zoulikha Belblidia & Johanna Shen & Iolanda Vendrell & Roman Fischer & Benedikt M. Kessler & Andrew N. Blackford, 2021. "The Bloom syndrome complex senses RPA-coated single-stranded DNA to restart stalled replication forks," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    3. Fumiko Esashi & Nicole Christ & Julian Gannon & Yilun Liu & Tim Hunt & Maria Jasin & Stephen C. West, 2005. "CDK-dependent phosphorylation of BRCA2 as a regulatory mechanism for recombinational repair," Nature, Nature, vol. 434(7033), pages 598-604, March.
    4. Luke A. Yates & Ricardo J. Aramayo & Nilisha Pokhrel & Colleen C. Caldwell & Joshua A. Kaplan & Rajika L. Perera & Maria Spies & Edwin Antony & Xiaodong Zhang, 2018. "A structural and dynamic model for the assembly of Replication Protein A on single-stranded DNA," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
    5. Aleksandra Lezaja & Andreas Panagopoulos & Yanlin Wen & Edison Carvalho & Ralph Imhof & Matthias Altmeyer, 2021. "RPA shields inherited DNA lesions for post-mitotic DNA synthesis," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    6. Alexey Bochkarev & Richard A. Pfuetzner & Aled M. Edwards & Lori Frappier, 1997. "Structure of the single-stranded-DNA-binding domain of replication protein A bound to DNA," Nature, Nature, vol. 385(6612), pages 176-181, January.
    7. Owen Addis Jones & Ankana Tiwari & Tomisin Olukoga & Alex Herbert & Kok-Lung Chan, 2019. "PLK1 facilitates chromosome biorientation by suppressing centromere disintegration driven by BLM-mediated unwinding and spindle pulling," Nature Communications, Nature, vol. 10(1), pages 1-17, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Sahiti Kuppa & Jaigeeth Deveryshetty & Rahul Chadda & Jenna R. Mattice & Nilisha Pokhrel & Vikas Kaushik & Angela Patterson & Nalini Dhingra & Sushil Pangeni & Marisa K. Sadauskas & Sajad Shiekh & Ham, 2022. "Rtt105 regulates RPA function by configurationally stapling the flexible domains," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    2. Aditi Mukherjee & Zakir Hossain & Esteban Erben & Shuai Ma & Jun Yong Choi & Hee-Sook Kim, 2023. "Identification of a small-molecule inhibitor that selectively blocks DNA-binding by Trypanosoma brucei replication protein A1," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    3. Zita Gál & Stavroula Boukoura & Kezia Catharina Oxe & Sara Badawi & Blanca Nieto & Lea Milling Korsholm & Sille Blangstrup Geisler & Ekaterina Dulina & Anna Vestergaard Rasmussen & Christina Dahl & We, 2024. "Hyper-recombination in ribosomal DNA is driven by long-range resection-independent RAD51 accumulation," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    4. Jiawei Ding & Xiangting Li & Jiangchuan Shen & Yiling Zhao & Shuchen Zhong & Luhua Lai & Hengyao Niu & Zhi Qi, 2023. "ssDNA accessibility of Rad51 is regulated by orchestrating multiple RPA dynamics," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    5. S. Cohen & A. Guenolé & I. Lazar & A. Marnef & T. Clouaire & D. V. Vernekar & N. Puget & V. Rocher & C. Arnould & M. Aguirrebengoa & M. Genais & N. Firmin & R. A. Shamanna & R. Mourad & V. A. Bohr & V, 2022. "A POLD3/BLM dependent pathway handles DSBs in transcribed chromatin upon excessive RNA:DNA hybrid accumulation," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    6. Yuxin Huang & Wenjing Li & Tzeh Foo & Jae-Hoon Ji & Bo Wu & Nozomi Tomimatsu & Qingming Fang & Boya Gao & Melissa Long & Jingfei Xu & Rouf Maqbool & Bipasha Mukherjee & Tengyang Ni & Salvador Alejo & , 2024. "DSS1 restrains BRCA2’s engagement with dsDNA for homologous recombination, replication fork protection, and R-loop homeostasis," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    7. Christopher B. Nelson & Samuel Rogers & Kaushik Roychoudhury & Yaw Sing Tan & Caroline J. Atkinson & Alexander P. Sobinoff & Christopher G. Tomlinson & Anton Hsu & Robert Lu & Eloise Dray & Michelle H, 2024. "The Eyes Absent family members EYA4 and EYA1 promote PLK1 activation and successful mitosis through tyrosine dephosphorylation," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    8. Youngho Kwon & Heike Rösner & Weixing Zhao & Platon Selemenakis & Zhuoling He & Ajinkya S. Kawale & Jeffrey N. Katz & Cody M. Rogers & Francisco E. Neal & Aida Badamchi Shabestari & Valdemaras Petrosi, 2023. "DNA binding and RAD51 engagement by the BRCA2 C-terminus orchestrate DNA repair and replication fork preservation," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    9. Robert Appleby & Luay Joudeh & Katie Cobbett & Luca Pellegrini, 2023. "Structural basis for stabilisation of the RAD51 nucleoprotein filament by BRCA2," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    10. Clément Madru & Markel Martínez-Carranza & Sébastien Laurent & Alessandra C. Alberti & Maelenn Chevreuil & Bertrand Raynal & Ahmed Haouz & Rémy A. Meur & Marc Delarue & Ghislaine Henneke & Didier Flam, 2023. "DNA-binding mechanism and evolution of replication protein A," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    11. Sarah R. Hengel & Katherine G. Oppenheimer & Chelsea M. Smith & Matthew A. Schaich & Hayley L. Rein & Julieta Martino & Kristie E. Darrah & Maggie Witham & Oluchi C. Ezekwenna & Kyle R. Burton & Benne, 2024. "The human Shu complex promotes RAD51 activity by modulating RPA dynamics on ssDNA," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    12. Seong-Su Han & Kuo-Kuang Wen & María L. García-Rubio & Marc S. Wold & Andrés Aguilera & Wojciech Niedzwiedz & Yatin M. Vyas, 2022. "WASp modulates RPA function on single-stranded DNA in response to replication stress and DNA damage," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    13. Ananya Acharya & Kristina Kasaciunaite & Martin Göse & Vera Kissling & Raphaël Guérois & Ralf Seidel & Petr Cejka, 2021. "Distinct RPA domains promote recruitment and the helicase-nuclease activities of Dna2," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    14. Liton Kumar Saha & Sourav Saha & Xi Yang & Shar-yin Naomi Huang & Yilun Sun & Ukhyun Jo & Yves Pommier, 2023. "Replication-associated formation and repair of human topoisomerase IIIα cleavage complexes," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    15. Owain J. Bryant & Filip Lastovka & Jessica Powell & Betty Y. -W. Chung, 2023. "The distinct translational landscapes of gram-negative Salmonella and gram-positive Listeria," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    16. Asuteka Nagao & Yui Nakanishi & Yutaro Yamaguchi & Yoshifumi Mishina & Minami Karoji & Takafumi Toya & Tomoya Fujita & Shintaro Iwasaki & Kenjyo Miyauchi & Yuriko Sakaguchi & Tsutomu Suzuki, 2023. "Quality control of protein synthesis in the early elongation stage," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    17. Aline Umuhire Juru & Rodolfo Ghirlando & Jinwei Zhang, 2024. "Structural basis of tRNA recognition by the widespread OB fold," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    18. Fajin Li & Jianhuo Fang & Yifan Yu & Sijia Hao & Qin Zou & Qinglin Zeng & Xuerui Yang, 2023. "Reanalysis of ribosome profiling datasets reveals a function of rocaglamide A in perturbing the dynamics of translation elongation via eIF4A," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    19. Nina Schmolka & Ino D. Karemaker & Richard Cardoso da Silva & Davide C. Recchia & Vincent Spegg & Jahnavi Bhaskaran & Michael Teske & Nathalie P. Wagenaar & Matthias Altmeyer & Tuncay Baubec, 2023. "Dissecting the roles of MBD2 isoforms and domains in regulating NuRD complex function during cellular differentiation," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    20. Chaoyou Xue & Sameer J. Salunkhe & Nozomi Tomimatsu & Ajinkya S. Kawale & Youngho Kwon & Sandeep Burma & Patrick Sung & Eric C. Greene, 2022. "Bloom helicase mediates formation of large single–stranded DNA loops during DNA end processing," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38711-2. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.