Your browser doesn't support javascript.
loading
Meiotic protein SYCP2 confers resistance to DNA-damaging agents through R-loop-mediated DNA repair.
Wang, Yumin; Gao, Boya; Zhang, Luyuan; Wang, Xudong; Zhu, Xiaolan; Yang, Haibo; Zhang, Fengqi; Zhu, Xueping; Zhou, Badi; Yao, Sean; Nagayama, Aiko; Lee, Sanghoon; Ouyang, Jian; Koh, Siang-Boon; Eisenhauer, Eric L; Zarrella, Dominique; Lu, Kate; Rueda, Bo R; Zou, Lee; Su, Xiaofeng A; Yeku, Oladapo; Ellisen, Leif W; Wang, Xiao-Song; Lan, Li.
Affiliation
  • Wang Y; Massachusetts General Hospital Cancer Center, Harvard Medical School, 13th Street, Charlestown, MA, 02129, USA.
  • Gao B; Massachusetts General Hospital Cancer Center, Harvard Medical School, 13th Street, Charlestown, MA, 02129, USA.
  • Zhang L; Department of Molecular Biology and Microbiology, Duke University School of Medicine, 213 Research Drive, Durham, NC, 27710, USA.
  • Wang X; Emory University School of Medicine, Atlanta, GA, 30322, USA.
  • Zhu X; Massachusetts General Hospital Cancer Center, Harvard Medical School, 13th Street, Charlestown, MA, 02129, USA.
  • Yang H; Massachusetts General Hospital Cancer Center, Harvard Medical School, 13th Street, Charlestown, MA, 02129, USA.
  • Zhang F; Massachusetts General Hospital Cancer Center, Harvard Medical School, 13th Street, Charlestown, MA, 02129, USA.
  • Zhu X; Massachusetts General Hospital Cancer Center, Harvard Medical School, 13th Street, Charlestown, MA, 02129, USA.
  • Zhou B; Department of Molecular Biology and Microbiology, Duke University School of Medicine, 213 Research Drive, Durham, NC, 27710, USA.
  • Yao S; Massachusetts General Hospital Cancer Center, Harvard Medical School, 13th Street, Charlestown, MA, 02129, USA.
  • Nagayama A; Massachusetts General Hospital Cancer Center, Harvard Medical School, 13th Street, Charlestown, MA, 02129, USA.
  • Lee S; Massachusetts General Hospital Cancer Center, Harvard Medical School, 13th Street, Charlestown, MA, 02129, USA.
  • Ouyang J; Massachusetts General Hospital Cancer Center, Harvard Medical School, 13th Street, Charlestown, MA, 02129, USA.
  • Koh SB; Ludwig Center at Harvard, Boston, MA, 02215, USA.
  • Eisenhauer EL; UPMC Hillman Cancer Center, University of Pittsburgh, 5117 Centre Ave, Pittsburgh, PA, 15232, USA.
  • Zarrella D; Department of Pathology, University of Pittsburgh, Pittsburgh, PA, 15232, USA.
  • Lu K; Department of Biomedical Informatics, University of Pittsburgh, Pittsburgh, PA, 15232, USA.
  • Rueda BR; Massachusetts General Hospital Cancer Center, Harvard Medical School, 13th Street, Charlestown, MA, 02129, USA.
  • Zou L; School of Cellular & Molecular Medicine, University of Bristol; University Walk, Bristol, BS8 1TD, UK.
  • Su XA; Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, 55 Fruit St, Massachusetts General Hospital, Boston, MA, 02114, USA.
  • Yeku O; Obstetrics, Gynecology and Reproductive Biology, Harvard Medical School, Boston, MA, 02115, USA.
  • Ellisen LW; Vincent Center for Reproductive Biology, Department of Obstetrics and Gynecology, 55 Fruit St, Massachusetts General Hospital, Boston, MA, 02114, USA.
  • Wang XS; David H. Koch Institute for Integrative Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
  • Lan L; Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, 55 Fruit St, Massachusetts General Hospital, Boston, MA, 02114, USA.
Nat Commun ; 15(1): 1568, 2024 Feb 21.
Article in En | MEDLINE | ID: mdl-38383600
ABSTRACT
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.
Subject(s)
Fulltext
Add to My VHL
Print
XML
PubMed Links
Search on Google

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: DNA Repair / R-Loop Structures Language: En Journal: Nat Commun Journal subject: BIOLOGIA / CIENCIA Year: 2024 Document type: Article Affiliation country:
Fulltext
Add to My VHL
Print
XML
PubMed Links
Search on Google

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: DNA Repair / R-Loop Structures Language: En Journal: Nat Commun Journal subject: BIOLOGIA / CIENCIA Year: 2024 Document type: Article Affiliation country: