Fusion of Nearby Inverted Repeats by a Replication-based Mechanism Leads to Formation of Dicentric and Acentric Chromosomes That Cause Genome Instability in Budding Yeast

Overview

Journal Genes Dev

Specialty Molecular Biology

Date 2009 Dec 17

PMID 20008936

Citations 50

Authors

Andrew L Paek

Salma Kaochar

Hope Jones

Aly Elezaby

Lisa Shanks

Ted Weinert

Affiliations

Soon will be listed here.

Abstract

Large-scale changes (gross chromosomal rearrangements [GCRs]) are common in genomes, and are often associated with pathological disorders. We report here that a specific pair of nearby inverted repeats in budding yeast fuse to form a dicentric chromosome intermediate, which then rearranges to form a translocation and other GCRs. We next show that fusion of nearby inverted repeats is general; we found that many nearby inverted repeats that are present in the yeast genome also fuse, as does a pair of synthetically constructed inverted repeats. Fusion occurs between inverted repeats that are separated by several kilobases of DNA and share >20 base pairs of homology. Finally, we show that fusion of inverted repeats, surprisingly, does not require genes involved in double-strand break (DSB) repair or genes involved in other repeat recombination events. We therefore propose that fusion may occur by a DSB-independent, DNA replication-based mechanism (which we term "faulty template switching"). Fusion of nearby inverted repeats to form dicentrics may be a major cause of instability in yeast and in other organisms.

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