岭南现代临床外科2026，Vol.26Issue(1)：10-21,12.DOI:10.3969/j.issn.1009-976X.2026.01.002
SNF5协同RNA解旋酶DDX5缓解R-loop积累维持肿瘤细胞基因组稳定性
SNF5 cooperates with RNA helicase DDX5 to resolve R-loop and maintain genome stability in tu-mor cells
摘要
Abstract
Objective To investigate the role and molecular mechanism of the chromatin remodeling factor SNF5 in tumor cell proliferation and genome stability maintenance.Methods An SNF5-knockout HeLa cell line was generated using CRISPR-Cas9 technology.Cell proliferation and cell cycle distribution were analyzed by EdU incorporation and flow cytometry,respectively.Colony formation assays were performed to evaluate cellular sensitivity to IR,HU,CPT,and MMC treatments.DNA fiber assays were used to assess DNA replication dynamics,and R-loop accumulation was detected by S9.6 immunofluores-cence.Potential SNF5-interacting proteins under replication stress were identified by IP-MS,followed by validation of SNF5-DDX5 interaction through co-immunoprecipitation(CoIP)and GST pull-down assay.Results Loss of SNF5 impaired DNA synthesis,increased the proportion of G1-phase cells,and mark-edly reduced proliferation of tumor cells,accompanied by enhanced sensitivity to DNA-damaging agents.DNA fiber assay revealed slowed replication fork progression in SNF5-deficient cells,while S9.6 staining indicated increased R-loop accumulation.Protein interaction assays confirmed that SNF5 physically asso-ciates with the RNA helicase DDX5,cooperating to alleviate R-loop accumulation under replication stress.Conclusion SNF5 promotes DNA replication and tumor cell proliferation by coordinating with DDX5 to resolve R-loop and maintain genomic stability.SNF5 deficiency leads to R-loop accumulation,replication impairment,and increased sensitivity to radio-and chemotherapy,supporting SNF5 as a potential tumor therapeutic target.关键词
SNF5/R-loop/RNA解旋酶家族/复制压力/基因组稳定性Key words
SNF5/DDX5/R-loop/DNA replication stress/genome stability分类
医药卫生引用本文复制引用
高源,谢晓娟,胡开顺..SNF5协同RNA解旋酶DDX5缓解R-loop积累维持肿瘤细胞基因组稳定性[J].岭南现代临床外科,2026,26(1):10-21,12.基金项目
国家自然科学基金(82373150 （）
82573408) （）
