University of Leicester
Browse
Telomere Dysfunction Triggers Palindrome Formation Independently of Double-Strand Break Repair Mechanisms.pdf (1.59 MB)

Telomere Dysfunction Triggers Palindrome Formation Independently of Double-Strand Break Repair Mechanisms.

Download (1.59 MB)
journal contribution
posted on 2016-11-23, 15:20 authored by V. Raykov, Marcus E. Marvin, Edward J. Louis, L. Maringele
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.

Funding

This work was supported by the Wellcome Trust (award no. 81164 to L.M.).

History

Citation

Genetics, 2016, 203 (4), pp. 1659-1668

Author affiliation

/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/MBSP Non-Medical Departments/Department of Genetics

Version

  • VoR (Version of Record)

Published in

Genetics

Publisher

Genetics Society of America

issn

0016-6731

eissn

1943-2631

Acceptance date

2016-06-04

Copyright date

2016

Available date

2016-11-23

Publisher version

http://www.genetics.org/content/203/4/1659

Notes

Supplemental material is available online at www.genetics.org/lookup/suppl/doi:10.1534/genetics.115.183020/-/DC1.

Language

en

Usage metrics

    University of Leicester Publications

    Categories

    Licence

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC