IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-31211-9.html
   My bibliography  Save this article

ZFP281-BRCA2 prevents R-loop accumulation during DNA replication

Author

Listed:
  • Yan Wang

    (Southeast University)

  • Binbin Ma

    (Tongji University)

  • Xiaoxu Liu

    (Southeast University)

  • Ge Gao

    (The University of Hong Kong)

  • Zhuanzhuan Che

    (Southeast University)

  • Menghan Fan

    (Southeast University)

  • Siyan Meng

    (Southeast University)

  • Xiru Zhao

    (Southeast University)

  • Rio Sugimura

    (The University of Hong Kong)

  • Hua Cao

    (Affiliated Hospital of Fujian Medical University)

  • Zhongjun Zhou

    (The University of Hong Kong)

  • Jing Xie

    (Tongji University)

  • Chengqi Lin

    (Affiliated Hospital of Fujian Medical University
    Southeast University
    Southeast University)

  • Zhuojuan Luo

    (Southeast University
    Southeast University)

Abstract

R-loops are prevalent in mammalian genomes and involved in many fundamental cellular processes. Depletion of BRCA2 leads to aberrant R-loop accumulation, contributing to genome instability. Here, we show that ZFP281 cooperates with BRCA2 in preventing R-loop accumulation to facilitate DNA replication in embryonic stem cells. ZFP281 depletion reduces PCNA levels on chromatin and impairs DNA replication. Mechanistically, we demonstrate that ZFP281 can interact with BRCA2, and that BRCA2 is enriched at G/C-rich promoters and requires both ZFP281 and PRC2 for its proper recruitment to the bivalent chromatin at the genome-wide scale. Furthermore, depletion of ZFP281 or BRCA2 leads to accumulation of R-loops over the bivalent regions, and compromises activation of the developmental genes by retinoic acid during stem cell differentiation. In summary, our results reveal that ZFP281 recruits BRCA2 to the bivalent chromatin regions to ensure proper progression of DNA replication through preventing persistent R-loops.

Suggested Citation

  • Yan Wang & Binbin Ma & Xiaoxu Liu & Ge Gao & Zhuanzhuan Che & Menghan Fan & Siyan Meng & Xiru Zhao & Rio Sugimura & Hua Cao & Zhongjun Zhou & Jing Xie & Chengqi Lin & Zhuojuan Luo, 2022. "ZFP281-BRCA2 prevents R-loop accumulation during DNA replication," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31211-9
    DOI: 10.1038/s41467-022-31211-9
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-31211-9
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-31211-9?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. Vaibhav Bhatia & Sonia I. Barroso & María L. García-Rubio & Emanuela Tumini & Emilia Herrera-Moyano & Andrés Aguilera, 2014. "BRCA2 prevents R-loop accumulation and associates with TREX-2 mRNA export factor PCID2," Nature, Nature, vol. 511(7509), pages 362-365, July.
    2. Konstantina Skourti-Stathaki & Kinga Kamieniarz-Gdula & Nicholas J. Proudfoot, 2014. "R-loops induce repressive chromatin marks over mammalian gene terminators," Nature, Nature, vol. 516(7531), pages 436-439, December.
    3. Qi-Long Ying & Jason Wray & Jennifer Nichols & Laura Batlle-Morera & Bradley Doble & James Woodgett & Philip Cohen & Austin Smith, 2008. "The ground state of embryonic stem cell self-renewal," Nature, Nature, vol. 453(7194), pages 519-523, May.
    4. Prasun Chakraborty & Jeffrey T. J. Huang & Kevin Hiom, 2018. "DHX9 helicase promotes R-loop formation in cells with impaired RNA splicing," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
    5. Luca Pellegrini & David S. Yu & Thomas Lo & Shubha Anand & MiYoung Lee & Tom L. Blundell & Ashok R. Venkitaraman, 2002. "Insights into DNA recombination from the structure of a RAD51–BRCA2 complex," Nature, Nature, vol. 420(6913), pages 287-293, November.
    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. Aleix Bayona-Feliu & Emilia Herrera-Moyano & Nibal Badra-Fajardo & Iván Galván-Femenía & María Eugenia Soler-Oliva & Andrés Aguilera, 2023. "The chromatin network helps prevent cancer-associated mutagenesis at transcription-replication conflicts," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. 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.
    3. Shiran Bar & Dan Vershkov & Gal Keshet & Elyad Lezmi & Naama Meller & Atilgan Yilmaz & Ofra Yanuka & Malka Nissim-Rafinia & Eran Meshorer & Talia Eldar-Geva & Nissim Benvenisty, 2021. "Identifying regulators of parental imprinting by CRISPR/Cas9 screening in haploid human embryonic stem cells," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    4. Robert Appleby & Luay Joudeh & Katie Cobbett & Luca Pellegrini, 2023. "Structural basis for stabilisation of the RAD51 nucleoprotein filament by BRCA2," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    5. Andrew Keniry & Natasha Jansz & Linden J. Gearing & Iromi Wanigasuriya & Joseph Chen & Christian M. Nefzger & Peter F. Hickey & Quentin Gouil & Joy Liu & Kelsey A. Breslin & Megan Iminitoff & Tamara B, 2022. "BAF complex-mediated chromatin relaxation is required for establishment of X chromosome inactivation," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    6. Arun Prakash Mishra & Suzanne A. Hartford & Sounak Sahu & Kimberly Klarmann & Rajani Kant Chittela & Kajal Biswas & Albert B. Jeon & Betty K. Martin & Sandra Burkett & Eileen Southon & Susan Reid & Ma, 2022. "BRCA2-DSS1 interaction is dispensable for RAD51 recruitment at replication-induced and meiotic DNA double strand breaks," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    7. Le Tran Phuc Khoa & Wentao Yang & Mengrou Shan & Li Zhang & Fengbiao Mao & Bo Zhou & Qiang Li & Rebecca Malcore & Clair Harris & Lili Zhao & Rajesh C. Rao & Shigeki Iwase & Sundeep Kalantry & Stephani, 2024. "Quiescence enables unrestricted cell fate in naive embryonic stem cells," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    8. Lihu Gong & Xiuli Liu & Lianying Jiao & Xin Yang & Andrew Lemoff & Xin Liu, 2022. "CK2-mediated phosphorylation of SUZ12 promotes PRC2 function by stabilizing enzyme active site," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    9. Gintautas Vainorius & Maria Novatchkova & Georg Michlits & Juliane Christina Baar & Cecilia Raupach & Joonsun Lee & Ramesh Yelagandula & Marius Wernig & Ulrich Elling, 2023. "Ascl1 and Ngn2 convert mouse embryonic stem cells to neurons via functionally distinct paths," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    10. Anna Malkowska & Christopher Penfold & Sophie Bergmann & Thorsten E. Boroviak, 2022. "A hexa-species transcriptome atlas of mammalian embryogenesis delineates metabolic regulation across three different implantation modes," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    11. Shengyong Yu & Chunhua Zhou & Jiangping He & Zhaokai Yao & Xingnan Huang & Bowen Rong & Hong Zhu & Shijie Wang & Shuyan Chen & Xialian Wang & Baomei Cai & Guoqing Zhao & Yuhan Chen & Lizhan Xiao & He , 2022. "BMP4 drives primed to naïve transition through PGC-like state," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    12. Valdemaras Petrosius & Pedro Aragon-Fernandez & Nil Üresin & Gergo Kovacs & Teeradon Phlairaharn & Benjamin Furtwängler & Jeff Op De Beeck & Sarah L. Skovbakke & Steffen Goletz & Simon Francis Thomsen, 2023. "Exploration of cell state heterogeneity using single-cell proteomics through sensitivity-tailored data-independent acquisition," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    13. Dasol Han & Guojing Liu & Yujeong Oh & Seyoun Oh & Seungbok Yang & Lori Mandjikian & Neha Rani & Maria C. Almeida & Kenneth S. Kosik & Jiwon Jang, 2023. "ZBTB12 is a molecular barrier to dedifferentiation in human pluripotent stem cells," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    14. Xingxing Ren & Qiuyuan Liu & Peirong Zhou & Tingyue Zhou & Decai Wang & Qiao Mei & Richard A. Flavell & Zhanju Liu & Mingsong Li & Wen Pan & Shu Zhu, 2024. "DHX9 maintains epithelial homeostasis by restraining R-loop-mediated genomic instability in intestinal stem cells," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    15. Timo N. Kohler & Joachim Jonghe & Anna L. Ellermann & Ayaka Yanagida & Michael Herger & Erin M. Slatery & Antonia Weberling & Clara Munger & Katrin Fischer & Carla Mulas & Alex Winkel & Connor Ross & , 2023. "Plakoglobin is a mechanoresponsive regulator of naive pluripotency," Nature Communications, Nature, vol. 14(1), pages 1-19, 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. Céline Labouesse & Bao Xiu Tan & Chibeza C. Agley & Moritz Hofer & Alexander K. Winkel & Giuliano G. Stirparo & Hannah T. Stuart & Christophe M. Verstreken & Carla Mulas & William Mansfield & Paul Ber, 2021. "StemBond hydrogels control the mechanical microenvironment for pluripotent stem cells," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
    18. Jiexiang Zhao & Ping Lu & Cong Wan & Yaping Huang & Manman Cui & Xinyan Yang & Yuqiong Hu & Yi Zheng & Ji Dong & Mei Wang & Shu Zhang & Zhaoting Liu & Shuhui Bian & Xiaoman Wang & Rui Wang & Shaofang , 2021. "Cell-fate transition and determination analysis of mouse male germ cells throughout development," Nature Communications, Nature, vol. 12(1), pages 1-20, December.
    19. Liang Chen & Yucong Wang & Jiamei Lin & Zhenxing Song & Qinwei Wang & Wenfang Zhao & Yan Wang & Xiaoyu Xiu & Yuqi Deng & Xiuzhi Li & Qiqi Li & Xiaolin Wang & Jingxin Li & Xu Liu & Kunpeng Liu & Jincon, 2022. "Exportin 4 depletion leads to nuclear accumulation of a subset of circular RNAs," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    20. Paraskevi Athanasouli & Martina Balli & Anchel Jaime-Soguero & Annekatrien Boel & Sofia Papanikolaou & Bernard K. Veer & Adrian Janiszewski & Tijs Vanhessche & Annick Francis & Youssef El Laithy & Ant, 2023. "The Wnt/TCF7L1 transcriptional repressor axis drives primitive endoderm formation by antagonizing naive and formative pluripotency," Nature Communications, Nature, vol. 14(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:13:y:2022:i:1:d:10.1038_s41467-022-31211-9. 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.