Yumin Wang, Boya Gao, Luyuan Zhang, Xudong Wang, Xiaolan Zhu, Haibo Yang, Fengqi Zhang, Xueping Zhu, Badi Zhou, Sean Yao, Aiko Nagayama, Sanghoon Lee, Jian Ouyang, Siang-Boon Koh, Eric L Eisenhauer, Dominique Zarrella, Kate Lu, Bo R Rueda, Lee Zou, Xiaofeng A Su, Oladapo Yeku, Leif W Ellisen, Xiao-Song Wang, Li Lan
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...
February 21, 2024: Nature Communications