title: Human CST Facilitates Genome-wide RAD51 Recruitment to GC-Rich Repetitive Sequences in Response to Replication Stress.
abstract: The telomeric CTC1/STN1/TEN1 (CST) complex has been implicated in promoting replication recovery under replication stress at genomic regions, yet its precise role is unclear. Here, we report that STN1 is enriched at GC-rich repetitive sequences genome-wide in response to hydroxyurea (HU)-induced replication stress. STN1 deficiency exacerbates the fragility of these sequences under replication stress, resulting in chromosome fragmentation. We find that upon fork stalling, CST proteins form distinct nuclear foci that colocalize with RAD51. Furthermore, replication stress induces physical association of CST with RAD51 in an ATR-dependent manner. Strikingly, CST deficiency diminishes HU-induced RAD51 foci formation and reduces RAD51 recruitment to telomeres and non-telomeric GC-rich fragile sequences. Collectively, our findings establish that CST promotes RAD51 recruitment to GC-rich repetitive sequences in response to replication stress to facilitate replication restart, thereby providing insights into the mechanism underlying genome stability maintenance.
authors.affiliation: Department of Biomedical Sciences, Elson S. Floyd College of Medicine, Washington State University, Spokane, WA 99210, USA.
authors.forename: Megan
authors.initials: M
authors.lastname: Chastain
authors.affiliation: Department of Biomedical Sciences, Elson S. Floyd College of Medicine, Washington State University, Spokane, WA 99210, USA.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Department of Biomedical Sciences, Elson S. Floyd College of Medicine, Washington State University, Spokane, WA 99210, USA.
authors.forename: Olga
authors.initials: O
authors.lastname: Shiva
authors.affiliation: Department of Biomedical Sciences, Elson S. Floyd College of Medicine, Washington State University, Spokane, WA 99210, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Fadri-Moskwik
authors.affiliation: School of Molecular Biosciences, Washington State University, Pullman, WA 99164, USA.
authors.forename: Leanne
authors.initials: L
authors.lastname: Whitmore
authors.affiliation: Department of Biomedical Sciences, Elson S. Floyd College of Medicine, Washington State University, Spokane, WA 99210, USA.
authors.forename: Pingping
authors.initials: P
authors.lastname: Jia
authors.affiliation: Department of Biomedical Sciences, Elson S. Floyd College of Medicine, Washington State University, Spokane, WA 99210, USA.
authors.forename: Xueyu
authors.initials: X
authors.lastname: Dai
authors.affiliation: Department of Biomedical Sciences, Elson S. Floyd College of Medicine, Washington State University, Spokane, WA 99210, USA.
authors.forename: Chenhui
authors.initials: C
authors.lastname: Huang
authors.affiliation: Department of Molecular and Experimental Medicine, Avera Cancer Institute, 1000 E 23rd Street, Suite 370, Sioux Falls, SD 57105, USA; Department of Pharmacy Practice, South Dakota State University, Brookings, SD 57007, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Ye
authors.affiliation: Department of Biomedical Sciences, Elson S. Floyd College of Medicine, Washington State University, Spokane, WA 99210, USA. Electronic address: wchai@wsu.edu.
authors.forename: Weihang
authors.initials: W
authors.lastname: Chai
mesh_terms: D045744:Cell Line, Tumor; D002873:Chromosome Fragility / Q000235:genetics; D053938:DNA Fragmentation; D004261:DNA Replication / Q000235:genetics*; D020862:GC Rich Sequence / Q000235:genetics*; D016678:Genome / Q000235:genetics; D042822:Genomic Instability / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D051135:Rad51 Recombinase / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics*; D016615:Telomere / Q000235:genetics; D059505:Telomere Homeostasis / Q000235:genetics; D034501:Telomere-Binding Proteins / Q000235:genetics*
chemical_list: C544945:Ctc1 protein, human; C544946:Stn1 protein, human; D034501:Telomere-Binding Proteins; C544947:Ten1 protein, human; D051135:Rad51 Recombinase
keywords: CTC1/STN1/TEN1; RAD51; genome stability; replication stress