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Nearby inverted repeats fuse to generate acentric and dicentric palindromic chromosomes by a replication template exchange mechanism.

Authors
Type
Published Article
Journal
Genes & Development
Publisher
Cold Spring Harbor Laboratory
Publication Date
Dec 28, 2009
Volume
23
Issue
24
Pages
2876–2886
Identifiers
DOI: 10.1101/gad.1863009
PMID: 20008937
PMCID: PMC2800087
Source
USPC - SET - SVS
License
Green

Abstract

Gene amplification plays important roles in the progression of cancer and contributes to acquired drug resistance during treatment. Amplification can initiate via dicentric palindromic chromosome production and subsequent breakage-fusion-bridge cycles. Here we show that, in fission yeast, acentric and dicentric palindromic chromosomes form by homologous recombination protein-dependent fusion of nearby inverted repeats, and that these fusions occur frequently when replication forks arrest within the inverted repeats. Genetic and molecular analyses suggest that these acentric and dicentric palindromic chromosomes arise not by previously described mechanisms, but by a replication template exchange mechanism that does not involve a DNA double-strand break. We thus propose an alternative mechanism for the generation of palindromic chromosomes dependent on replication fork arrest at closely spaced inverted repeats.

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