IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-45947-z.html
   My bibliography  Save this article

RTF2 controls replication repriming and ribonucleotide excision at the replisome

Author

Listed:
  • Brooke A. Conti

    (The Rockefeller University)

  • Penelope D. Ruiz

    (The Rockefeller University)

  • Cayla Broton

    (The Rockefeller University)

  • Nicolas J. Blobel

    (The Rockefeller University)

  • Molly C. Kottemann

    (The Rockefeller University)

  • Sunandini Sridhar

    (The Rockefeller University)

  • Francis P. Lach

    (The Rockefeller University)

  • Tom F. Wiley

    (The Rockefeller University)

  • Nanda K. Sasi

    (The Rockefeller University)

  • Thomas Carroll

    (The Rockefeller University)

  • Agata Smogorzewska

    (The Rockefeller University)

Abstract

DNA replication through a challenging genomic landscape is coordinated by the replisome, which must adjust to local conditions to provide appropriate replication speed and respond to lesions that hinder its progression. We have previously shown that proteasome shuttle proteins, DNA Damage Inducible 1 and 2 (DDI1/2), regulate Replication Termination Factor 2 (RTF2) levels at stalled replisomes, allowing fork stabilization and restart. Here, we show that during unperturbed replication, RTF2 regulates replisome localization of RNase H2, a heterotrimeric enzyme that removes RNA from RNA-DNA heteroduplexes. RTF2, like RNase H2, is essential for mammalian development and maintains normal replication speed. However, persistent RTF2 and RNase H2 at stalled replication forks prevent efficient replication restart, which is dependent on PRIM1, the primase component of DNA polymerase α-primase. Our data show a fundamental need for RTF2-dependent regulation of replication-coupled ribonucleotide removal and reveal the existence of PRIM1-mediated direct replication restart in mammalian cells.

Suggested Citation

  • Brooke A. Conti & Penelope D. Ruiz & Cayla Broton & Nicolas J. Blobel & Molly C. Kottemann & Sunandini Sridhar & Francis P. Lach & Tom F. Wiley & Nanda K. Sasi & Thomas Carroll & Agata Smogorzewska, 2024. "RTF2 controls replication repriming and ribonucleotide excision at the replisome," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45947-z
    DOI: 10.1038/s41467-024-45947-z
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-45947-z
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-024-45947-z?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. Michal Zimmermann & Olga Murina & Martin A. M. Reijns & Angelo Agathanggelou & Rachel Challis & Žygimantė Tarnauskaitė & Morwenna Muir & Adeline Fluteau & Michael Aregger & Andrea McEwan & Wei Yuan & , 2018. "CRISPR screens identify genomic ribonucleotides as a source of PARP-trapping lesions," Nature, Nature, vol. 559(7713), pages 285-289, July.
    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. Inés Paniagua & Zainab Tayeh & Mattia Falcone & Santiago Hernández Pérez & Aurora Cerutti & Jacqueline J. L. Jacobs, 2022. "MAD2L2 promotes replication fork protection and recovery in a shieldin-independent and REV3L-dependent manner," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    2. Natasha Ramakrishnan & Tyler M. Weaver & Lindsey N. Aubuchon & Ayda Woldegerima & Taylor Just & Kevin Song & Alessandro Vindigni & Bret D. Freudenthal & Priyanka Verma, 2024. "Nucleolytic processing of abasic sites underlies PARP inhibitor hypersensitivity in ALC1-deficient BRCA mutant cancer cells," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    3. Nazanin Esmaeili Anvar & Chenchu Lin & Xingdi Ma & Lori L. Wilson & Ryan Steger & Annabel K. Sangree & Medina Colic & Sidney H. Wang & John G. Doench & Traver Hart, 2024. "Efficient gene knockout and genetic interaction screening using the in4mer CRISPR/Cas12a multiplex knockout platform," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    4. Anders Mälarstig & Felix Grassmann & Leo Dahl & Marios Dimitriou & Dianna McLeod & Marike Gabrielson & Karl Smith-Byrne & Cecilia E. Thomas & Tzu-Hsuan Huang & Simon K. G. Forsberg & Per Eriksson & Mi, 2023. "Evaluation of circulating plasma proteins in breast cancer using Mendelian randomisation," Nature Communications, Nature, vol. 14(1), pages 1-9, December.
    5. Zuzana Machacova & Katarina Chroma & David Lukac & Iva Protivankova & Pavel Moudry, 2024. "DNA polymerase α-primase facilitates PARP inhibitor-induced fork acceleration and protects BRCA1-deficient cells against ssDNA gaps," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    6. Xabier Vergara & Anna G. Manjón & Marcel Haas & Ben Morris & Ruben Schep & Christ Leemans & Anoek Friskes & Roderick L. Beijersbergen & Mathijs A. Sanders & René H. Medema & Bas Steensel, 2024. "Widespread chromatin context-dependencies of DNA double-strand break repair proteins," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    7. Petra Brugge & Sarah C. Moser & Ivan Bièche & Petra Kristel & Sabrina Ibadioune & Alexandre Eeckhoutte & Roebi Bruijn & Eline Burg & Catrin Lutz & Stefano Annunziato & Julian Ruiter & Julien Masliah P, 2023. "Homologous recombination deficiency derived from whole-genome sequencing predicts platinum response in triple-negative breast cancers," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    8. Natalie Schindler & Matthias Tonn & Vanessa Kellner & Jia Jun Fung & Arianna Lockhart & Olga Vydzhak & Thomas Juretschke & Stefanie Möckel & Petra Beli & Anton Khmelinskii & Brian Luke, 2023. "Genetic requirements for repair of lesions caused by single genomic ribonucleotides in S phase," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    9. Takuya Tsujino & Tomoaki Takai & Kunihiko Hinohara & Fu Gui & Takeshi Tsutsumi & Xiao Bai & Chenkui Miao & Chao Feng & Bin Gui & Zsofia Sztupinszki & Antoine Simoneau & Ning Xie & Ladan Fazli & Xuesen, 2023. "CRISPR screens reveal genetic determinants of PARP inhibitor sensitivity and resistance in prostate cancer," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    10. Demis Menolfi & Brian J. Lee & Hanwen Zhang & Wenxia Jiang & Nicole E. Bowen & Yunyue Wang & Junfei Zhao & Antony Holmes & Steven Gershik & Raul Rabadan & Baek Kim & Shan Zha, 2023. "ATR kinase supports normal proliferation in the early S phase by preventing replication resource exhaustion," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    11. Abhishek Bharadwaj Sharma & Muhammad Khairul Ramlee & Joel Kosmin & Martin R. Higgs & Amy Wolstenholme & George E. Ronson & Dylan Jones & Daniel Ebner & Noor Shamkhi & David Sims & Paul W. G. Wijnhove, 2023. "C16orf72/HAPSTR1/TAPR1 functions with BRCA1/Senataxin to modulate replication-associated R-loops and confer resistance to PARP disruption," Nature Communications, Nature, vol. 14(1), pages 1-15, 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:15:y:2024:i:1:d:10.1038_s41467-024-45947-z. 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.