Meiotic protein SYCP2 confers resistance to DNA-damaging agents through R-loop-mediated DNA repair

  1. Wang, Yumin ORCID logo
  2. Gao, Boya
  3. Zhang, Luyuan
  4. Wang, Xudong
  5. ZHU, XIAOLAN ORCID logo
  6. Yang, Haibo
  7. Zhang, Fengqi
  8. Zhu, Xueping
  9. Zhou, Badi
  10. Yao, Sean
  11. Nagayama, Aiko ORCID logo
  12. Lee, Sanghoon
  13. Ouyang, Jian
  14. Koh, Siang-Boon ORCID logo
  15. Eisenhauer, Eric L.
  16. Zarrella, Dominique
  17. Lu, Kate
  18. Rueda, Bo ORCID logo
  19. Zou, Lee ORCID logo
  20. Su, Xiaofeng A.
  21. Yeku, Oladapo ORCID logo
  22. Ellisen, Leif ORCID logo
  23. Wang, Xiaosong ORCID logo
  24. Lan, Li

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WeightNameValue
1000 Titel
  • Meiotic protein SYCP2 confers resistance to DNA-damaging agents through R-loop-mediated DNA repair
1000 Autor/in
  1. Wang, Yumin |
  2. Gao, Boya |
  3. Zhang, Luyuan |
  4. Wang, Xudong |
  5. ZHU, XIAOLAN |
  6. Yang, Haibo |
  7. Zhang, Fengqi |
  8. Zhu, Xueping |
  9. Zhou, Badi |
  10. Yao, Sean |
  11. Nagayama, Aiko |
  12. Lee, Sanghoon |
  13. Ouyang, Jian |
  14. Koh, Siang-Boon |
  15. Eisenhauer, Eric L. |
  16. Zarrella, Dominique |
  17. Lu, Kate |
  18. Rueda, Bo |
  19. Zou, Lee |
  20. Su, Xiaofeng A. |
  21. Yeku, Oladapo |
  22. Ellisen, Leif |
  23. Wang, Xiaosong |
  24. Lan, Li |
1000 Erscheinungsjahr 2024
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2024-02-21
1000 Erschienen in
1000 Quellenangabe
  • 15(1):1568
1000 Copyrightjahr
  • 2024
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1038/s41467-024-45693-2 |
1000 Ergänzendes Material
  • https://www.nature.com/articles/s41467-024-45693-2#Sec28 |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • Drugs targeting the DNA damage response (DDR) are widely used in cancer therapy, but resistance to these drugs remains a major clinical challenge. Here, we show that SYCP2, a meiotic protein in the synaptonemal complex, is aberrantly and commonly expressed in breast and ovarian cancers and associated with broad resistance to DDR drugs. Mechanistically, SYCP2 enhances the repair of DNA double-strand breaks (DSBs) through transcription-coupled homologous recombination (TC-HR). SYCP2 promotes R-loop formation at DSBs and facilitates RAD51 recruitment independently of BRCA1. SYCP2 loss impairs RAD51 localization, reduces TC-HR, and renders tumors sensitive to PARP and topoisomerase I (TOP1) inhibitors. Furthermore, our studies of two clinical cohorts find that SYCP2 overexpression correlates with breast cancer resistance to antibody-conjugated TOP1 inhibitor and ovarian cancer resistance to platinum treatment. Collectively, our data suggest that SYCP2 confers cancer cell resistance to DNA-damaging agents by stimulating R-loop-mediated DSB repair, offering opportunities to improve DDR therapy.
1000 Sacherschließung
lokal Breast cancer
lokal DNA damage response
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
  1. https://orcid.org/0000-0003-4167-9411|https://frl.publisso.de/adhoc/uri/R2FvLCBCb3lh|https://frl.publisso.de/adhoc/uri/WmhhbmcsIEx1eXVhbg==|https://frl.publisso.de/adhoc/uri/V2FuZywgWHVkb25n|https://orcid.org/0000-0002-0499-8045|https://frl.publisso.de/adhoc/uri/WWFuZywgSGFpYm8=|https://frl.publisso.de/adhoc/uri/WmhhbmcsIEZlbmdxaQ==|https://frl.publisso.de/adhoc/uri/Wmh1LCBYdWVwaW5n|https://frl.publisso.de/adhoc/uri/WmhvdSwgQmFkaQ==|https://frl.publisso.de/adhoc/uri/WWFvLCBTZWFu|https://orcid.org/0000-0002-7453-8132|https://frl.publisso.de/adhoc/uri/TGVlLCBTYW5naG9vbg==|https://frl.publisso.de/adhoc/uri/T3V5YW5nLCBKaWFu|https://orcid.org/0000-0002-5494-3800|https://frl.publisso.de/adhoc/uri/RWlzZW5oYXVlciwgRXJpYyBMLg==|https://frl.publisso.de/adhoc/uri/WmFycmVsbGEsIERvbWluaXF1ZQ==|https://frl.publisso.de/adhoc/uri/THUsIEthdGU=|https://orcid.org/0000-0001-9489-8699|https://orcid.org/0000-0003-3094-1058|https://frl.publisso.de/adhoc/uri/U3UsIFhpYW9mZW5nIEEu|https://orcid.org/0000-0002-6319-1647|https://orcid.org/0000-0003-0444-7910|https://orcid.org/0000-0002-2570-7139|https://frl.publisso.de/adhoc/uri/TGFuLCBMaQ==
1000 Label
1000 Förderer
  1. National Institutes of Health |
  2. Nile Albright Research Foundation |
  3. Vincent Memorial Hospital Foundation |
1000 Fördernummer
  1. GM118833; CA282939; CA181368; CA183976; 1R21CA237964; R01 GM076388; CA197779
  2. -
  3. -
1000 Förderprogramm
  1. -
  2. -
  3. -
1000 Dateien
1000 Förderung
  1. 1000 joinedFunding-child
    1000 Förderer National Institutes of Health |
    1000 Förderprogramm -
    1000 Fördernummer GM118833; CA282939; CA181368; CA183976; 1R21CA237964; R01 GM076388; CA197779
  2. 1000 joinedFunding-child
    1000 Förderer Nile Albright Research Foundation |
    1000 Förderprogramm -
    1000 Fördernummer -
  3. 1000 joinedFunding-child
    1000 Förderer Vincent Memorial Hospital Foundation |
    1000 Förderprogramm -
    1000 Fördernummer -
1000 Objektart article
1000 Beschrieben durch
1000 @id frl:6473230.rdf
1000 Erstellt am 2024-02-21T10:46:20.714+0100
1000 Erstellt von 284
1000 beschreibt frl:6473230
1000 Bearbeitet von 317
1000 Zuletzt bearbeitet 2024-02-21T12:29:22.995+0100
1000 Objekt bearb. Wed Feb 21 12:29:03 CET 2024
1000 Vgl. frl:6473230
1000 Oai Id
  1. oai:frl.publisso.de:frl:6473230 |
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