Telomere Dysfunction Triggers Palindrome Formation Independently of Double-Strand Break Repair Mechanisms
| Autor: | Vasil, Raykov, Marcus E, Marvin, Edward J, Louis, Laura, Maringele |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
telomere
Rev3 DNA End-Joining Repair Saccharomyces cerevisiae Proteins Inverted Repeat Sequences palindrome Recombinational DNA Repair Telomere Homeostasis Dnl4 DNA-Directed DNA Polymerase Saccharomyces cerevisiae Investigations Rad52 DNA Repair and Recombination Protein Genome Integrity and Transmission DNA Ligase ATP polymerase zeta Rad52 Rad51 Rad51 Recombinase Homologous Recombination Telomerase |
| Zdroj: | Genetics |
| ISSN: | 1943-2631 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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