IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-36968-1.html
   My bibliography  Save this article

DNA replication initiation factor RECQ4 possesses a role in antagonizing DNA replication initiation

Author

Listed:
  • Xiaohua Xu

    (Thermo Fisher Scientific)

  • Chou-Wei Chang

    (Vesigen Therapeutics)

  • Min Li

    (City of Hope)

  • Kenneth Omabe

    (City of Hope)

  • Nhung Le

    (City of Hope)

  • Yi-Hsuan Chen

    (University of Southern California)

  • Feng Liang

    (University of Southern California)

  • Yilun Liu

    (City of Hope)

Abstract

Deletion of the conserved C-terminus of the Rothmund-Thomson syndrome helicase RECQ4 is highly tumorigenic. However, while the RECQ4 N-terminus is known to facilitate DNA replication initiation, the function of its C-terminus remains unclear. Using an unbiased proteomic approach, we identify an interaction between the RECQ4 N-terminus and the anaphase-promoting complex/cyclosome (APC/C) on human chromatin. We further show that this interaction stabilizes APC/C co-activator CDH1 and enhances APC/C-dependent degradation of the replication inhibitor Geminin, allowing replication factors to accumulate on chromatin. In contrast, the function is blocked by the RECQ4 C-terminus, which binds to protein inhibitors of APC/C. A cancer-prone, C-terminal-deleted RECQ4 mutation increases origin firing frequency, accelerates G1/S transition, and supports abnormally high DNA content. Our study reveals a role of the human RECQ4 C-terminus in antagonizing its N-terminus, thereby suppressing replication initiation, and this suppression is impaired by oncogenic mutations.

Suggested Citation

  • Xiaohua Xu & Chou-Wei Chang & Min Li & Kenneth Omabe & Nhung Le & Yi-Hsuan Chen & Feng Liang & Yilun Liu, 2023. "DNA replication initiation factor RECQ4 possesses a role in antagonizing DNA replication initiation," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36968-1
    DOI: 10.1038/s41467-023-36968-1
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-36968-1
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-36968-1?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. Xin Yang & Robinson Triboulet & Qi Liu & Erdem Sendinc & Richard I. Gregory, 2022. "Exon junction complex shapes the m6A epitranscriptome," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    2. Sang-Min Jang & Ya Zhang & Koichi Utani & Haiqing Fu & Christophe E. Redon & Anna B. Marks & Owen K. Smith & Catherine J. Redmond & Adrian M. Baris & Danielle A. Tulchinsky & Mirit I. Aladjem, 2018. "The replication initiation determinant protein (RepID) modulates replication by recruiting CUL4 to chromatin," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
    3. Tarig Bashir & N. Valerio Dorrello & Virginia Amador & Daniele Guardavaccaro & Michele Pagano, 2004. "Control of the SCFSkp2–Cks1 ubiquitin ligase by the APC/CCdh1 ubiquitin ligase," Nature, Nature, vol. 428(6979), pages 190-193, March.
    4. Sebastian Kaiser & Florian Sauer & Caroline Kisker, 2017. "The structural and functional characterization of human RecQ4 reveals insights into its helicase mechanism," Nature Communications, Nature, vol. 8(1), pages 1-12, August.
    5. Alessandro Magli & June Baik & Pruthvi Pota & Carolina Ortiz Cordero & Il-Youp Kwak & Daniel J. Garry & Paul E. Love & Brian D. Dynlacht & Rita C. R. Perlingeiro, 2019. "Pax3 cooperates with Ldb1 to direct local chromosome architecture during myogenic lineage specification," Nature Communications, Nature, vol. 10(1), pages 1-17, December.
    6. Suyang Zhang & Thomas Tischer & David Barford, 2019. "Cyclin A2 degradation during the spindle assembly checkpoint requires multiple binding modes to the APC/C," Nature Communications, Nature, vol. 10(1), pages 1-16, 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. Sang Bae Lee & Luciano Garofano & Aram Ko & Fulvio D’Angelo & Brulinda Frangaj & Danika Sommer & Qiwen Gan & KyeongJin Kim & Timothy Cardozo & Antonio Iavarone & Anna Lasorella, 2022. "Regulated interaction of ID2 with the anaphase-promoting complex links progression through mitosis with reactivation of cell-type-specific transcription," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    2. Ji Min Lee & Henrik M. Hammarén & Mikhail M. Savitski & Sung Hee Baek, 2023. "Control of protein stability by post-translational modifications," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    3. 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.
    4. P Acera Mateos & A J Sethi & A Ravindran & A Srivastava & K Woodward & S Mahmud & M Kanchi & M Guarnacci & J Xu & Z W S Yuen & Y Zhou & A Sneddon & W Hamilton & J Gao & L M Starrs & R Hayashi & V Wick, 2024. "Prediction of m6A and m5C at single-molecule resolution reveals a transcriptome-wide co-occurrence of RNA modifications," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    5. Mingsen Li & Huaxing Huang & Bofeng Wang & Shaoshuai Jiang & Huizhen Guo & Liqiong Zhu & Siqi Wu & Jiafeng Liu & Li Wang & Xihong Lan & Wang Zhang & Jin Zhu & Fuxi Li & Jieying Tan & Zhen Mao & Chunqi, 2022. "Comprehensive 3D epigenomic maps define limbal stem/progenitor cell function and identity," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    6. Jingxuan Xu & Xiang Xu & Dandan Huang & Yawen Luo & Lin Lin & Xuemei Bai & Yang Zheng & Qian Yang & Yu Cheng & An Huang & Jingyi Shi & Xiaochen Bo & Jin Gu & Hebing Chen, 2024. "A comprehensive benchmarking with interpretation and operational guidance for the hierarchy of topologically associating domains," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    7. Christopher Thomas & Benjamin Wetherall & Mark D. Levasseur & Rebecca J. Harris & Scott T. Kerridge & Jonathan M. G. Higgins & Owen R. Davies & Suzanne Madgwick, 2021. "A prometaphase mechanism of securin destruction is essential for meiotic progression in mouse oocytes," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    8. Anna C. Papageorgiou & Michaela Pospisilova & Jakub Cibulka & Raghib Ashraf & Christopher A. Waudby & Pavel Kadeřávek & Volha Maroz & Karel Kubicek & Zbynek Prokop & Lumir Krejci & Konstantinos Tripsi, 2023. "Recognition and coacervation of G-quadruplexes by a multifunctional disordered region in RECQ4 helicase," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    9. Zhiyuan Luo & Qilian Ma & Shan Sun & Ningning Li & Hongfeng Wang & Zheng Ying & Shengdong Ke, 2023. "Exon-intron boundary inhibits m6A deposition, enabling m6A distribution hallmark, longer mRNA half-life and flexible protein coding," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    10. Guanqun Wang & Haoxuan Li & Chang Ye & Kayla He & Shun Liu & Bochen Jiang & Ruiqi Ge & Boyang Gao & Jiangbo Wei & Yutao Zhao & Aixuan Li & Di Zhang & Jianhua Zhang & Chuan He, 2024. "Quantitative profiling of m6A at single base resolution across the life cycle of rice and Arabidopsis," Nature Communications, Nature, vol. 15(1), pages 1-14, 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.

    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_s41467-023-36968-1. 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.