title: Timeless protection of telomeres.
abstract: The DNA replication machinery encounters problems at numerous genomic regions that are inherently difficult to replicate. These genomic regions include telomeres, which contain repetitive DNA and telomere-binding proteins. If not properly regulated, replication of such genomic regions can result in DNA damage, leading to genomic instability. Studies implicated a role of Timeless-related proteins at difficult-to-replicate genomic regions, including telomeres. However, how these proteins maintain telomeres was elusive. In a recent report, we described the role of Swi1, a Timeless-related protein, in telomere maintenance in fission yeast. We demonstrated that Swi1 is required for proper replication of repeat DNA sequences at telomeres. We also showed that Swi1-deficient cells utilize recombination-based ALT (alternative lengthening of telomeres)-like mechanisms to maintain telomeres in the absence of telomerase. Here, we highlight these findings and present additional data to discuss the role of Swi1Timelessin telomere protection and ALT prevention.
authors.affiliation: Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, 245 N. 15th Street, Philadelphia, PA, 19102, USA.|The Scripps Research Institute, La Jolla, CA, 92037, USA.
authors.forename: Mariana C
authors.initials: MC
authors.lastname: Gadaleta
authors.affiliation: Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, 245 N. 15th Street, Philadelphia, PA, 19102, USA.|Universitat Pompeu Fabra, 08003, Barcelona, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: González-Medina
authors.affiliation: Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, 245 N. 15th Street, Philadelphia, PA, 19102, USA. enoguchi@drexelmed.edu.
authors.forename: Eishi
authors.initials: E
authors.lastname: Noguchi
mesh_terms: D002352:Carrier Proteins; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D004249:DNA Damage; D004261:DNA Replication; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D016678:Genome; D023281:Genomics; D011485:Protein Binding; D045522:Recombinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011995:Recombination, Genetic; D012091:Repetitive Sequences, Nucleic Acid; D019098:Telomerase / Q000378:metabolism; D016615:Telomere / Q000235:genetics* / Q000378:metabolism*; D059505:Telomere Homeostasis
chemical_list: D002352:Carrier Proteins; D002868:Chromosomal Proteins, Non-Histone; D045522:Recombinases; D019098:Telomerase; D004259:DNA-Directed DNA Polymerase
keywords: ALT; Alternative lengthening of telomeres; Cancer; FPC; Fork protection complex; Genomic integrity; Myb/SANT; Repeat DNA; Replication fork; Swi1; Tbf1; Telomeres; Timeless