IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-39332-5.html
   My bibliography  Save this article

ATR kinase supports normal proliferation in the early S phase by preventing replication resource exhaustion

Author

Listed:
  • Demis Menolfi

    (Columbia University)

  • Brian J. Lee

    (Columbia University)

  • Hanwen Zhang

    (Columbia University)

  • Wenxia Jiang

    (Columbia University)

  • Nicole E. Bowen

    (Emory University School of Medicine)

  • Yunyue Wang

    (Columbia University)

  • Junfei Zhao

    (Columbia University)

  • Antony Holmes

    (Columbia University)

  • Steven Gershik

    (Columbia University)

  • Raul Rabadan

    (Columbia University)

  • Baek Kim

    (Emory University School of Medicine)

  • Shan Zha

    (Columbia University
    Columbia University
    Columbia University
    Columbia University)

Abstract

The ATR kinase, which coordinates cellular responses to DNA replication stress, is also essential for the proliferation of normal unstressed cells. Although its role in the replication stress response is well defined, the mechanisms by which ATR supports normal cell proliferation remain elusive. Here, we show that ATR is dispensable for the viability of G0-arrested naïve B cells. However, upon cytokine-induced proliferation, Atr-deficient B cells initiate DNA replication efficiently, but by mid-S phase they display dNTP depletion, fork stalling, and replication failure. Nonetheless, productive DNA replication and dNTP levels can be restored in Atr-deficient cells by suppressing origin firing, such as partial inhibition of CDC7 and CDK1 kinase activities. Together, these findings indicate that ATR supports the proliferation of normal unstressed cells by tempering the pace of origin firing during the early S phase to avoid exhaustion of dNTPs and importantly also other replication factors.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39332-5
    DOI: 10.1038/s41467-023-39332-5
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-39332-5
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-39332-5?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. Catherine T. Yan & Cristian Boboila & Ellen Kris Souza & Sonia Franco & Thomas R. Hickernell & Michael Murphy & Sunil Gumaste & Mark Geyer & Ali A. Zarrin & John P. Manis & Klaus Rajewsky & Frederick , 2007. "IgH class switching and translocations use a robust non-classical end-joining pathway," Nature, Nature, vol. 449(7161), pages 478-482, September.
    2. 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.
    3. Massimo Lopes & Cecilia Cotta-Ramusino & Achille Pellicioli & Giordano Liberi & Paolo Plevani & Marco Muzi-Falconi & Carol S. Newlon & Marco Foiani, 2001. "The DNA replication checkpoint response stabilizes stalled replication forks," Nature, Nature, vol. 412(6846), pages 557-561, August.
    4. José Antonio Tercero & John F. X. Diffley, 2001. "Regulation of DNA replication fork progression through damaged DNA by the Mec1/Rad53 checkpoint," Nature, Nature, vol. 412(6846), pages 553-557, August.
    5. Jan M. Suski & Nalin Ratnayeke & Marcin Braun & Tian Zhang & Vladislav Strmiska & Wojciech Michowski & Geylani Can & Antoine Simoneau & Konrad Snioch & Mikolaj Cup & Caitlin M. Sullivan & Xiaoji Wu & , 2022. "CDC7-independent G1/S transition revealed by targeted protein degradation," Nature, Nature, vol. 605(7909), pages 357-365, May.
    6. Morgane Macheret & Thanos D. Halazonetis, 2018. "Intragenic origins due to short G1 phases underlie oncogene-induced DNA replication stress," Nature, Nature, vol. 555(7694), pages 112-116, March.
    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. Elias Einig & Chao Jin & Valentina Andrioletti & Boris Macek & Nikita Popov, 2023. "RNAPII-dependent ATM signaling at collisions with replication forks," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    2. Samuel Hume & Claudia P. Grou & Pauline Lascaux & Vincenzo D’Angiolella & Arnaud J. Legrand & Kristijan Ramadan & Grigory L. Dianov, 2021. "The NUCKS1-SKP2-p21/p27 axis controls S phase entry," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    3. Taichi Igarashi & Marianne Mazevet & Takaaki Yasuhara & Kimiyoshi Yano & Akifumi Mochizuki & Makoto Nishino & Tatsuya Yoshida & Yukihiro Yoshida & Nobuhiko Takamatsu & Akihide Yoshimi & Kouya Shiraish, 2023. "An ATR-PrimPol pathway confers tolerance to oncogenic KRAS-induced and heterochromatin-associated replication stress," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    4. Shaun Scaramuzza & Rebecca M. Jones & Martina Muste Sadurni & Alicja Reynolds-Winczura & Divyasree Poovathumkadavil & Abigail Farrell & Toyoaki Natsume & Patricia Rojas & Cyntia Fernandez Cuesta & Mas, 2023. "TRAIP resolves DNA replication-transcription conflicts during the S-phase of unperturbed cells," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    5. 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.
    6. 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.
    7. Estelle Vincendeau & Wenming Wei & Xuefei Zhang & Cyril Planchais & Wei Yu & Hélène Lenden-Hasse & Thomas Cokelaer & Juliana Pipoli da Fonseca & Hugo Mouquet & David J. Adams & Frederick W. Alt & Step, 2022. "SHLD1 is dispensable for 53BP1-dependent V(D)J recombination but critical for productive class switch recombination," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    8. 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.
    9. Lorenzo Corazzi & Vivien S. Ionasz & Sergej Andrejev & Li-Chin Wang & Athanasios Vouzas & Marco Giaisi & Giulia Di Muzio & Boyu Ding & Anna J. M. Marx & Jonas Henkenjohann & Michael M. Allers & David , 2024. "Linear interaction between replication and transcription shapes DNA break dynamics at recurrent DNA break Clusters," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    10. 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.
    11. Karl-Uwe Reusswig & Julia Bittmann & Martina Peritore & Mathilde Courtes & Benjamin Pardo & Michael Wierer & Matthias Mann & Boris Pfander, 2022. "Unscheduled DNA replication in G1 causes genome instability and damage signatures indicative of replication collisions," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    12. 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.
    13. 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.
    14. Yijiang Xu & Hang Zhou & Ginell Post & Hong Zan & Paolo Casali, 2022. "Rad52 mediates class-switch DNA recombination to IgD," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    15. 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.
    16. Bertrand Theulot & Laurent Lacroix & Jean-Michel Arbona & Gael A. Millot & Etienne Jean & Corinne Cruaud & Jade Pellet & Florence Proux & Magali Hennion & Stefan Engelen & Arnaud Lemainque & Benjamin , 2022. "Genome-wide mapping of individual replication fork velocities using nanopore sequencing," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    17. Ting Zhang & Carsten Künne & Dong Ding & Stefan Günther & Xinyue Guo & Yonggang Zhou & Xuejun Yuan & Thomas Braun, 2022. "Replication collisions induced by de-repressed S-phase transcription are connected with malignant transformation of adult stem cells," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    18. Silvia Peripolli & Leticia Meneguello & Chiara Perrod & Tanya Singh & Harshil Patel & Sazia T. Rahman & Koshiro Kiso & Peter Thorpe & Vincenzo Calvanese & Cosetta Bertoli & Robertus A. M. de Bruin, 2024. "Oncogenic c-Myc induces replication stress by increasing cohesins chromatin occupancy in a CTCF-dependent manner," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    19. Martin Andrs & Henriette Stoy & Barbora Boleslavska & Nagaraja Chappidi & Radhakrishnan Kanagaraj & Zuzana Nascakova & Shruti Menon & Satyajeet Rao & Anna Oravetzova & Jana Dobrovolna & Kalpana Surend, 2023. "Excessive reactive oxygen species induce transcription-dependent replication stress," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    20. Nicholas A Willis & Arvind Panday & Erin E Duffey & Ralph Scully, 2018. "Rad51 recruitment and exclusion of non-homologous end joining during homologous recombination at a Tus/Ter mammalian replication fork barrier," PLOS Genetics, Public Library of Science, vol. 14(7), pages 1-28, July.

    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_s41467-023-39332-5. 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.