Expansion of Interstitial Telomeric Sequences in Yeast.

Cell Rep
Authors
Keywords
Abstract

Telomeric repeats located within chromosomes are called interstitial telomeric sequences (ITSs). They are polymorphic in length and are likely hotspots for initiation of chromosomal rearrangements that have been linked to human disease. Using our S. cerevisiae system to study repeat-mediated genome instability, we have previously shown that yeast telomeric (Ytel) repeats induce various gross chromosomal rearrangements (GCR) when their G-rich strands serve as the lagging strand template for replication (G orientation). Here, we show that interstitial Ytel repeats in the opposite C orientation prefer to expand rather than cause GCR. A tract of eight Ytel repeats expands at a rate of 4 × 10(-4) per replication, ranking them among the most expansion-prone DNA microsatellites. A candidate-based genetic analysis implicates both post-replication repair and homologous recombination pathways in the expansion process. We propose a model for Ytel repeat expansions and discuss its applications for genome instability and alternative telomere lengthening (ALT).

Year of Publication
2015
Journal
Cell Rep
Volume
13
Issue
8
Pages
1545-51
Date Published
2015 Nov 24
ISSN
2211-1247
URL
DOI
10.1016/j.celrep.2015.10.023
PubMed ID
26586439
PubMed Central ID
PMC4662878
Links
Grant list
P01 GM105473 / GM / NIGMS NIH HHS / United States
R01 GM060987 / GM / NIGMS NIH HHS / United States
GM105473 / GM / NIGMS NIH HHS / United States
GM60987 / GM / NIGMS NIH HHS / United States