End joining at Caenorhabditis elegans telomeres.

Abstract:

:Critically shortened telomeres can be subjected to DNA repair events that generate end-to-end chromosome fusions. The resulting dicentric chromosomes can enter breakage-fusion-bridge cycles, thereby impeding elucidation of the structures of the initial fusion events and a mechanistic understanding of their genesis. Current models for the molecular basis of fusion of critically shortened, uncapped telomeres rely on PCR assays that typically capture fusion breakpoints created by direct ligation of chromosome ends. Here we use independent approaches that rely on distinctive features of Caenorhabditis elegans to study the frequency of direct end-to-end chromosome fusion in telomerase mutants: (1) holocentric chromosomes that allow for genetic isolation of stable end-to-end fusions and (2) unique subtelomeric sequences that allow for thorough PCR analysis of samples of genomic DNA harboring multiple end-to-end fusions. Surprisingly, only a minority of end-to-end fusion events resulted from direct end joining with no additional genome rearrangements. We also demonstrate that deficiency for the C. elegans Ku DNA repair heterodimer does not affect telomere length or cause synthetic effects in the absence of telomerase.

journal_name

Genetics

journal_title

Genetics

authors

Lowden MR,Meier B,Lee TW,Hall J,Ahmed S

doi

10.1534/genetics.108.089920

subject

Has Abstract

pub_date

2008-10-01 00:00:00

pages

741-54

issue

2

eissn

0016-6731

issn

1943-2631

pii

genetics.108.089920

journal_volume

180

pub_type

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