End Resection Initiates Genomic Instability in the Absence of Telomerase

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 2003 Nov 13

PMID 14612391

Citations 49

Authors

Jennifer A Hackett

Carol W Greider

Affiliations

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Abstract

Telomere dysfunction causes genomic instability. However, the mechanism that initiates this instability when telomeres become short is unclear. We measured the mutation rate and loss of heterozygosity along a chromosome arm in diploid yeast that lacked telomerase to distinguish between mechanisms for the initiation of instability. Sequence loss was localized near chromosome ends in the absence of telomerase but not after breakage of a dicentric chromosome. In the absence of telomerase, the increase in mutation rate is dependent on the exonuclease Exo1p. Thus, exonucleolytic end resection, rather than chromosome fusion and breakage, is the primary mechanism that initiates genomic instability when telomeres become short.

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