IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-37341-y.html
   My bibliography  Save this article

Excessive reactive oxygen species induce transcription-dependent replication stress

Author

Listed:
  • Martin Andrs

    (Institute of Molecular Genetics of the Czech Academy of Sciences
    University of Zurich)

  • Henriette Stoy

    (University of Zurich)

  • Barbora Boleslavska

    (Institute of Molecular Genetics of the Czech Academy of Sciences
    Charles University in Prague)

  • Nagaraja Chappidi

    (University of Zurich
    Technische Universität Dresden)

  • Radhakrishnan Kanagaraj

    (University of Westminster
    University of Bedfordshire
    Sathyabama Institute of Science and Technology)

  • Zuzana Nascakova

    (Institute of Molecular Genetics of the Czech Academy of Sciences
    University of Zurich)

  • Shruti Menon

    (University of Zurich
    University of California San Francisco (UCSF))

  • Satyajeet Rao

    (University of Zurich)

  • Anna Oravetzova

    (Institute of Molecular Genetics of the Czech Academy of Sciences
    Charles University in Prague)

  • Jana Dobrovolna

    (Institute of Molecular Genetics of the Czech Academy of Sciences)

  • Kalpana Surendranath

    (University of Westminster
    Sathyabama Institute of Science and Technology)

  • Massimo Lopes

    (University of Zurich)

  • Pavel Janscak

    (Institute of Molecular Genetics of the Czech Academy of Sciences
    University of Zurich)

Abstract

Elevated levels of reactive oxygen species (ROS) reduce replication fork velocity by causing dissociation of the TIMELESS-TIPIN complex from the replisome. Here, we show that ROS generated by exposure of human cells to the ribonucleotide reductase inhibitor hydroxyurea (HU) promote replication fork reversal in a manner dependent on active transcription and formation of co-transcriptional RNA:DNA hybrids (R-loops). The frequency of R-loop-dependent fork stalling events is also increased after TIMELESS depletion or a partial inhibition of replicative DNA polymerases by aphidicolin, suggesting that this phenomenon is due to a global replication slowdown. In contrast, replication arrest caused by HU-induced depletion of deoxynucleotides does not induce fork reversal but, if allowed to persist, leads to extensive R-loop-independent DNA breakage during S-phase. Our work reveals a link between oxidative stress and transcription-replication interference that causes genomic alterations recurrently found in human cancer.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-37341-y
    DOI: 10.1038/s41467-023-37341-y
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-37341-y
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-37341-y?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. Sofija Mijic & Ralph Zellweger & Nagaraja Chappidi & Matteo Berti & Kurt Jacobs & Karun Mutreja & Sebastian Ursich & Arnab Ray Chaudhuri & Andre Nussenzweig & Pavel Janscak & Massimo Lopes, 2017. "Replication fork reversal triggers fork degradation in BRCA2-defective cells," Nature Communications, Nature, vol. 8(1), pages 1-11, December.
    2. Julie Rageul & Jennifer J. Park & Ping Ping Zeng & Eun-A Lee & Jihyeon Yang & Sunyoung Hwang & Natalie Lo & Alexandra S. Weinheimer & Orlando D. Schärer & Jung-Eun Yeo & Hyungjin Kim, 2020. "SDE2 integrates into the TIMELESS-TIPIN complex to protect stalled replication forks," Nature Communications, Nature, vol. 11(1), pages 1-16, December.
    3. 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.
    4. Sheroy Minocherhomji & Songmin Ying & Victoria A. Bjerregaard & Sara Bursomanno & Aiste Aleliunaite & Wei Wu & Hocine W. Mankouri & Huahao Shen & Ying Liu & Ian D. Hickson, 2015. "Replication stress activates DNA repair synthesis in mitosis," Nature, Nature, vol. 528(7581), pages 286-290, December.
    5. Yaqun Teng & Tribhuwan Yadav & Meihan Duan & Jun Tan & Yufei Xiang & Boya Gao & Jianquan Xu & Zhuobin Liang & Yang Liu & Satoshi Nakajima & Yi Shi & Arthur S. Levine & Lee Zou & Li Lan, 2018. "ROS-induced R loops trigger a transcription-coupled but BRCA1/2-independent homologous recombination pathway through CSB," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Miho M. Suzuki & Kenta Iijima & Koichi Ogami & Keiko Shinjo & Yoshiteru Murofushi & Jingqi Xie & Xuebing Wang & Yotaro Kitano & Akira Mamiya & Yuji Kibe & Tatsunori Nishimura & Fumiharu Ohka & Ryuta S, 2023. "TUG1-mediated R-loop resolution at microsatellite loci as a prerequisite for cancer cell proliferation," Nature Communications, Nature, vol. 14(1), pages 1-20, December.

    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. Frederick Richards & Marta J. Llorca-Cardenosa & Jamie Langton & Sara C. Buch-Larsen & Noor F. Shamkhi & Abhishek Bharadwaj Sharma & Michael L. Nielsen & Nicholas D. Lakin, 2023. "Regulation of Rad52-dependent replication fork recovery through serine ADP-ribosylation of PolD3," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    2. Thomas E. Wilson & Samreen Ahmed & Amanda Winningham & Thomas W. Glover, 2024. "Replication stress induces POLQ-mediated structural variant formation throughout common fragile sites after entry into mitosis," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    3. Liana Goehring & Sarah Keegan & Sudipta Lahiri & Wenxin Xia & Michael Kong & Judit Jimenez-Sainz & Dipika Gupta & Ronny Drapkin & Ryan B. Jensen & Duncan J. Smith & Eli Rothenberg & David Fenyö & Tony, 2024. "Dormant origin firing promotes head-on transcription-replication conflicts at transcription termination sites in response to BRCA2 deficiency," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    4. 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.
    5. 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.
    6. 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.
    7. Arindam Datta & Kajal Biswas & Joshua A. Sommers & Haley Thompson & Sanket Awate & Claudia M. Nicolae & Tanay Thakar & George-Lucian Moldovan & Robert H. Shoemaker & Shyam K. Sharan & Robert M. Brosh, 2021. "WRN helicase safeguards deprotected replication forks in BRCA2-mutated cancer cells," Nature Communications, Nature, vol. 12(1), pages 1-22, December.
    8. 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.
    9. 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.
    10. 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.
    11. Wei Wu & Szymon A. Barwacz & Rahul Bhowmick & Katrine Lundgaard & Marisa M. Gonçalves Dinis & Malgorzata Clausen & Masato T. Kanemaki & Ying Liu, 2023. "Mitotic DNA synthesis in response to replication stress requires the sequential action of DNA polymerases zeta and delta in human cells," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    12. Anastasiya Kishkevich & Sanjeeta Tamang & Michael O. Nguyen & Judith Oehler & Elena Bulmaga & Christos Andreadis & Carl A. Morrow & Manisha Jalan & Fekret Osman & Matthew C. Whitby, 2022. "Rad52’s DNA annealing activity drives template switching associated with restarted DNA replication," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    13. Anastasia Hale & Ashna Dhoonmoon & Joshua Straka & Claudia M. Nicolae & George-Lucian Moldovan, 2023. "Multi-step processing of replication stress-derived nascent strand DNA gaps by MRE11 and EXO1 nucleases," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    14. George E. Ronson & Katarzyna Starowicz & Elizabeth J. Anthony & Ann Liza Piberger & Lucy C. Clarke & Alexander J. Garvin & Andrew D. Beggs & Celina M. Whalley & Matthew J. Edmonds & James F. J. Beesle, 2023. "Mechanisms of synthetic lethality between BRCA1/2 and 53BP1 deficiencies and DNA polymerase theta targeting," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    15. Manisha Jalan & Aman Sharma & Xin Pei & Nils Weinhold & Erika S. Buechelmaier & Yingjie Zhu & Sana Ahmed-Seghir & Abhirami Ratnakumar & Melody Bona & Niamh McDermott & Joan Gomez-Aguilar & Kyrie S. An, 2024. "RAD52 resolves transcription-replication conflicts to mitigate R-loop induced genome instability," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    16. Haibo Yang & Emily M. Lachtara & Xiaojuan Ran & Jessica Hopkins & Parasvi S. Patel & Xueping Zhu & Yao Xiao & Laiyee Phoon & Boya Gao & Lee Zou & Michael S. Lawrence & Li Lan, 2023. "The RNA m5C modification in R-loops as an off switch of Alt-NHEJ," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    17. Daniela Muoio & Natalie Laspata & Rachel L. Dannenberg & Caroline Curry & Simone Darkoa-Larbi & Mark Hedglin & Shikhar Uttam & Elise Fouquerel, 2024. "PARP2 promotes Break Induced Replication-mediated telomere fragility in response to replication stress," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    18. Wezley C. Griffin & David R. McKinzey & Kathleen N. Klinzing & Rithvik Baratam & Achini Eliyapura & Michael A. Trakselis, 2022. "A multi-functional role for the MCM8/9 helicase complex in maintaining fork integrity during replication stress," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    19. 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.
    20. Zhihua Kang & Pan Fu & Allen L. Alcivar & Haiqing Fu & Christophe Redon & Tzeh Keong Foo & Yamei Zuo & Caiyong Ye & Ryan Baxley & Advaitha Madireddy & Remi Buisson & Anja-Katrin Bielinsky & Lee Zou & , 2021. "BRCA2 associates with MCM10 to suppress PRIMPOL-mediated repriming and single-stranded gap formation after DNA damage," Nature Communications, Nature, vol. 12(1), pages 1-12, 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_s41467-023-37341-y. 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.