IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v12y2021i1d10.1038_s41467-021-26172-4.html
   My bibliography  Save this article

The regulatory landscape of the human HPF1- and ARH3-dependent ADP-ribosylome

Author

Listed:
  • Ivo A. Hendriks

    (University of Copenhagen)

  • Sara C. Buch-Larsen

    (University of Copenhagen)

  • Evgeniia Prokhorova

    (University of Oxford)

  • Jonas D. Elsborg

    (University of Copenhagen)

  • Alexandra K.L.F.S. Rebak

    (University of Copenhagen)

  • Kang Zhu

    (University of Oxford)

  • Dragana Ahel

    (University of Oxford)

  • Claudia Lukas

    (University of Copenhagen)

  • Ivan Ahel

    (University of Oxford)

  • Michael L. Nielsen

    (University of Copenhagen)

Abstract

Despite the involvement of Poly(ADP-ribose) polymerase-1 (PARP1) in many important biological pathways, the target residues of PARP1-mediated ADP-ribosylation remain ambiguous. To explicate the ADP-ribosylation regulome, we analyze human cells depleted for key regulators of PARP1 activity, histone PARylation factor 1 (HPF1) and ADP-ribosylhydrolase 3 (ARH3). Using quantitative proteomics, we characterize 1,596 ADP-ribosylation sites, displaying up to 1000-fold regulation across the investigated knockout cells. We find that HPF1 and ARH3 inversely and homogenously regulate the serine ADP-ribosylome on a proteome-wide scale with consistent adherence to lysine-serine-motifs, suggesting that targeting is independent of HPF1 and ARH3. Notably, we do not detect an HPF1-dependent target residue switch from serine to glutamate/aspartate under the investigated conditions. Our data support the notion that serine ADP-ribosylation mainly exists as mono-ADP-ribosylation in cells, and reveal a remarkable degree of histone co-modification with serine ADP-ribosylation and other post-translational modifications.

Suggested Citation

  • Ivo A. Hendriks & Sara C. Buch-Larsen & Evgeniia Prokhorova & Jonas D. Elsborg & Alexandra K.L.F.S. Rebak & Kang Zhu & Dragana Ahel & Claudia Lukas & Ivan Ahel & Michael L. Nielsen, 2021. "The regulatory landscape of the human HPF1- and ARH3-dependent ADP-ribosylome," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26172-4
    DOI: 10.1038/s41467-021-26172-4
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-021-26172-4
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-021-26172-4?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. Dea Slade & Mark S. Dunstan & Eva Barkauskaite & Ria Weston & Pierre Lafite & Neil Dixon & Marijan Ahel & David Leys & Ivan Ahel, 2011. "The structure and catalytic mechanism of a poly(ADP-ribose) glycohydrolase," Nature, Nature, vol. 477(7366), pages 616-620, September.
    2. Marcin J. Suskiewicz & Florian Zobel & Tom E. H. Ogden & Pietro Fontana & Antonio Ariza & Ji-Chun Yang & Kang Zhu & Lily Bracken & William J. Hawthorne & Dragana Ahel & David Neuhaus & Ivan Ahel, 2020. "HPF1 completes the PARP active site for DNA damage-induced ADP-ribosylation," Nature, Nature, vol. 579(7800), pages 598-602, March.
    3. Silvija Bilokapic & Marcin J. Suskiewicz & Ivan Ahel & Mario Halic, 2020. "Bridging of DNA breaks activates PARP2–HPF1 to modify chromatin," Nature, Nature, vol. 585(7826), pages 609-613, September.
    4. Kathrin Nowak & Florian Rosenthal & Tobias Karlberg & Mareike Bütepage & Ann-Gerd Thorsell & Birgit Dreier & Jonas Grossmann & Jens Sobek & Ralph Imhof & Bernhard Lüscher & Herwig Schüler & Andreas Pl, 2020. "Engineering Af1521 improves ADP-ribose binding and identification of ADP-ribosylated proteins," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    5. Hana Hanzlikova & Evgeniia Prokhorova & Katerina Krejcikova & Zuzana Cihlarova & Ilona Kalasova & Jan Kubovciak & Jana Sachova & Richard Hailstone & Jan Brazina & Shereen Ghosh & Sebahattin Cirak & Jo, 2020. "Pathogenic ARH3 mutations result in ADP-ribose chromatin scars during DNA strand break repair," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
    6. Qian Chen & Muzaffer Ahmad Kassab & Françoise Dantzer & Xiaochun Yu, 2018. "PARP2 mediates branched poly ADP-ribosylation in response to DNA damage," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
    7. Arnab Ray Chaudhuri & Elsa Callen & Xia Ding & Ewa Gogola & Alexandra A. Duarte & Ji-Eun Lee & Nancy Wong & Vanessa Lafarga & Jennifer A. Calvo & Nicholas J. Panzarino & Sam John & Amanda Day & Anna V, 2016. "Replication fork stability confers chemoresistance in BRCA-deficient cells," Nature, Nature, vol. 535(7612), pages 382-387, July.
    8. Christopher J. Lord & Alan Ashworth, 2012. "The DNA damage response and cancer therapy," Nature, Nature, vol. 481(7381), pages 287-294, January.
    9. Arnab Ray Chaudhuri & Elsa Callen & Xia Ding & Ewa Gogola & Alexandra A. Duarte & Ji-Eun Lee & Nancy Wong & Vanessa Lafarga & Jennifer A. Calvo & Nicholas J. Panzarino & Sam John & Amanda Day & Anna V, 2016. "Erratum: Replication fork stability confers chemoresistance in BRCA-deficient cells," Nature, Nature, vol. 539(7629), pages 456-456, November.
    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. 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. Zita Fábián & Ellen S. Kakulidis & Ivo A. Hendriks & Ulrike Kühbacher & Nicolai B. Larsen & Marta Oliva-Santiago & Junhui Wang & Xueyuan Leng & A. Barbara Dirac-Svejstrup & Jesper Q. Svejstrup & Micha, 2024. "PARP1-dependent DNA-protein crosslink repair," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    3. Edoardo José Longarini & Ivan Matić, 2024. "Preserving ester-linked modifications reveals glutamate and aspartate mono-ADP-ribosylation by PARP1 and its reversal by PARG," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    4. Pietro Fontana & Sara C. Buch-Larsen & Osamu Suyari & Rebecca Smith & Marcin J. Suskiewicz & Kira Schützenhofer & Antonio Ariza & Johannes Gregor Matthias Rack & Michael L. Nielsen & Ivan Ahel, 2023. "Serine ADP-ribosylation in Drosophila provides insights into the evolution of reversible ADP-ribosylation signalling," Nature Communications, Nature, vol. 14(1), pages 1-18, 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. Pietro Fontana & Sara C. Buch-Larsen & Osamu Suyari & Rebecca Smith & Marcin J. Suskiewicz & Kira Schützenhofer & Antonio Ariza & Johannes Gregor Matthias Rack & Michael L. Nielsen & Ivan Ahel, 2023. "Serine ADP-ribosylation in Drosophila provides insights into the evolution of reversible ADP-ribosylation signalling," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    2. 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.
    3. Nikolaos Parisis & Pablo D. Dans & Muhammad Jbara & Balveer Singh & Diane Schausi-Tiffoche & Diego Molina-Serrano & Isabelle Brun-Heath & Denisa Hendrychová & Suman Kumar Maity & Diana Buitrago & Rafa, 2023. "Histone H3 serine-57 is a CHK1 substrate whose phosphorylation affects DNA repair," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    4. 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.
    5. Luka Bacic & Guillaume Gaullier & Jugal Mohapatra & Guanzhong Mao & Klaus Brackmann & Mikhail Panfilov & Glen Liszczak & Anton Sabantsev & Sebastian Deindl, 2024. "Asymmetric nucleosome PARylation at DNA breaks mediates directional nucleosome sliding by ALC1," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
    6. 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.
    7. Cuige Zhu & Mari Iwase & Ziqian Li & Faliang Wang & Annabel Quinet & Alessandro Vindigni & Jieya Shao, 2022. "Profilin-1 regulates DNA replication forks in a context-dependent fashion by interacting with SNF2H and BOD1L," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    8. Marie-France Langelier & Ramya Billur & Aleksandr Sverzhinsky & Ben E. Black & John M. Pascal, 2021. "HPF1 dynamically controls the PARP1/2 balance between initiating and elongating ADP-ribose modifications," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    9. Antonios Revythis & Anu Limbu & Christos Mikropoulos & Aruni Ghose & Elisabet Sanchez & Matin Sheriff & Stergios Boussios, 2022. "Recent Insights into PARP and Immuno-Checkpoint Inhibitors in Epithelial Ovarian Cancer," IJERPH, MDPI, vol. 19(14), pages 1-19, July.
    10. Simon D. Schwarz & Jianming Xu & Kapila Gunasekera & David Schürmann & Cathrine B. Vågbø & Elena Ferrari & Geir Slupphaug & Michael O. Hottiger & Primo Schär & Roland Steinacher, 2024. "Covalent PARylation of DNA base excision repair proteins regulates DNA demethylation," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    11. Ramona N. Moro & Uddipta Biswas & Suhas S. Kharat & Filip D. Duzanic & Prosun Das & Maria Stavrou & Maria C. Raso & Raimundo Freire & Arnab Ray Chaudhuri & Shyam K. Sharan & Lorenza Penengo, 2023. "Interferon restores replication fork stability and cell viability in BRCA-defective cells via ISG15," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    12. Vera M. Kissling & Giordano Reginato & Eliana Bianco & Kristina Kasaciunaite & Janny Tilma & Gea Cereghetti & Natalie Schindler & Sung Sik Lee & Raphaël Guérois & Brian Luke & Ralf Seidel & Petr Cejka, 2022. "Mre11-Rad50 oligomerization promotes DNA double-strand break repair," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    13. Ashna Dhoonmoon & Claudia M. Nicolae & George-Lucian Moldovan, 2022. "The KU-PARP14 axis differentially regulates DNA resection at stalled replication forks by MRE11 and EXO1," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    14. Nagham Ghaddar & Yves Corda & Pierre Luciano & Martina Galli & Ylli Doksani & Vincent Géli, 2023. "The COMPASS subunit Spp1 protects nascent DNA at the Tus/Ter replication fork barrier by limiting DNA availability to nucleases," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    15. 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.
    16. Anne Margriet Heijink & Colin Stok & David Porubsky & Eleni Maria Manolika & Jurrian K. Kanter & Yannick P. Kok & Marieke Everts & H. Rudolf Boer & Anastasia Audrey & Femke J. Bakker & Elles Wierenga , 2022. "Sister chromatid exchanges induced by perturbed replication can form independently of BRCA1, BRCA2 and RAD51," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    17. Zu Ye & Shengfeng Xu & Yin Shi & Xueqian Cheng & Yuan Zhang & Sunetra Roy & Sarita Namjoshi & Michael A. Longo & Todd M. Link & Katharina Schlacher & Guang Peng & Dihua Yu & Bin Wang & John A. Tainer , 2024. "GRB2 stabilizes RAD51 at reversed replication forks suppressing genomic instability and innate immunity against cancer," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    18. Tanay Thakar & Ashna Dhoonmoon & Joshua Straka & Emily M. Schleicher & Claudia M. Nicolae & George-Lucian Moldovan, 2022. "Lagging strand gap suppression connects BRCA-mediated fork protection to nucleosome assembly through PCNA-dependent CAF-1 recycling," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    19. Maria Dilia Palumbieri & Chiara Merigliano & Daniel González-Acosta & Danina Kuster & Jana Krietsch & Henriette Stoy & Thomas Känel & Svenja Ulferts & Bettina Welter & Joël Frey & Cyril Doerdelmann & , 2023. "Nuclear actin polymerization rapidly mediates replication fork remodeling upon stress by limiting PrimPol activity," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    20. Kate E. Coleman & Yandong Yin & Sarah Kit Leng Lui & Sarah Keegan & David Fenyo & Duncan J. Smith & Eli Rothenberg & Tony T. Huang, 2022. "USP1-trapping lesions as a source of DNA replication stress and genomic instability," Nature Communications, Nature, vol. 13(1), pages 1-19, 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:12:y:2021:i:1:d:10.1038_s41467-021-26172-4. 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.