title: Telomere Dysfunction Triggers Palindrome Formation Independently of Double-Strand Break Repair Mechanisms.
abstract: Inverted chromosome duplications or palindromes are linked with genetic disorders and malignant transformation. They are considered by-products of DNA double-strand break (DSB) repair: the homologous recombination (HR) and the nonhomologous end joining (NHEJ). Palindromes near chromosome ends are often triggered by telomere losses. An important question is to what extent their formation depends upon DSB repair mechanisms. Here we addressed this question using yeast genetics and comparative genomic hybridization. We induced palindrome formation by passaging cells lacking any form of telomere maintenance (telomerase and telomere recombination). Surprisingly, we found that DNA ligase 4, essential for NHEJ, did not make a significant contribution to palindrome formation induced by telomere losses. Moreover RAD51, important for certain HR-derived mechanisms, had little effect. Furthermore RAD52, which is essential for HR in yeast, appeared to decrease the number of palindromes in cells proliferating without telomeres. This study also uncovered an important role for Rev3 and Rev7 (but not for Pol32) subunits of polymerase ζ in the survival of cells undergoing telomere losses and forming palindromes. We propose a model called short-inverted repeat-induced synthesis in which DNA synthesis, rather than DSB repair, drives the inverted duplication triggered by telomere dysfunction.
authors.affiliation: Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne, NE2 4HH, United Kingdom.
authors.forename: Vasil
authors.initials: V
authors.lastname: Raykov
authors.affiliation: Department of Genetics, Centre for Genetic Architecture of Complex Traits, University of Leicester, LE1 7RH, United Kingdom.
authors.forename: Marcus E
authors.initials: ME
authors.lastname: Marvin
authors.affiliation: Department of Genetics, Centre for Genetic Architecture of Complex Traits, University of Leicester, LE1 7RH, United Kingdom.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Louis
authors.affiliation: Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne, NE2 4HH, United Kingdom Laura.Maringele@ncl.ac.uk.
authors.forename: Laura
authors.initials: L
authors.lastname: Maringele
mesh_terms: D059766:DNA End-Joining Repair / Q000235:genetics; D000072481:DNA Ligase ATP / Q000235:genetics*; D004259:DNA-Directed DNA Polymerase / Q000235:genetics*; D059765:Homologous Recombination / Q000235:genetics; D055029:Inverted Repeat Sequences / Q000235:genetics*; D051135:Rad51 Recombinase / Q000235:genetics; D051721:Rad52 DNA Repair and Recombination Protein / Q000235:genetics; D059767:Recombinational DNA Repair / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics*; D019098:Telomerase / Q000235:genetics*; D016615:Telomere; D059505:Telomere Homeostasis
chemical_list: C000607891:DNL4 protein, S cerevisiae; C497197:RAD52 protein, S cerevisiae; C092219:REV7 protein, S cerevisiae; D051721:Rad52 DNA Repair and Recombination Protein; D029701:Saccharomyces cerevisiae Proteins; C495151:RAD51 protein, S cerevisiae; D051135:Rad51 Recombinase; D019098:Telomerase; D004259:DNA-Directed DNA Polymerase; C092602:REV3 protein, S cerevisiae; D000072481:DNA Ligase ATP
keywords: Dnl4; Rad51; Rad52; Rev3; palindrome; polymerase zeta; telomere