title: Human CST has independent functions during telomere duplex replication and C-strand fill-in.
abstract: Human CST (CTC1-STN1-TEN1) is an RPA-like complex that is needed for efficient replication through the telomere duplex and genome-wide replication restart after fork stalling. Here, we show that STN1/CST has a second function in telomere replication during G-overhang maturation. Analysis of overhang structure after STN1 depletion revealed normal kinetics for telomerase-mediated extension in S phase but a delay in subsequent overhang shortening. This delay resulted from a defect in C-strand fill-in. Short telomeres exhibited the fill-in defect but normal telomere duplex replication, indicating that STN1/CST functions independently in these processes. Our work also indicates that the requirement for STN1/CST in telomere duplex replication correlates with increasing telomere length and replication stress. Our results provide direct evidence that STN1/CST participates in C-strand fill-in. They also demonstrate that STN1/CST participates in two mechanistically separate steps during telomere replication and identify CST as a replication factor that solves diverse replication-associated problems.
authors.affiliation: Department of Cancer and Cell Biology, University of Cincinnati, Cincinnati, OH 45267-0521, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.forename: Jason A
authors.initials: JA
authors.lastname: Stewart
authors.forename: Christopher
authors.initials: C
authors.lastname: Kasbek
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhao
authors.forename: Woodring E
authors.initials: WE
authors.lastname: Wright
authors.forename: Carolyn M
authors.initials: CM
authors.lastname: Price
mesh_terms: D004247:DNA / Q000378:metabolism; D004256:DNA Polymerase I / Q000378:metabolism; D004261:DNA Replication; D016195:G2 Phase; D045325:HCT116 Cells; D006367:HeLa Cells; D006801:Humans; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D016196:S Phase; D019098:Telomerase / Q000378:metabolism; D016615:Telomere / Q000378:metabolism*; D034501:Telomere-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D034741:RNA, Small Interfering; C544946:Stn1 protein, human; D034501:Telomere-Binding Proteins; D004247:DNA; D019098:Telomerase; D004256:DNA Polymerase I