Inverted DNA Repeats Channel Repair of Distant Double-Strand Breaks into Chromatid Fusions and Chromosomal Rearrangements

Kelly VanHulle; Francene J Lemoine; Vidhya Narayanan; Brandon Downing; Krista Hull; Christy McCullough; Melissa Bellinger; Kirill Lobachev; Thomas D Petes; Anna Malkova

doi:10.1128/MCB.01740-06

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Inverted DNA Repeats Channel Repair of Distant Double-Strand Breaks into Chromatid Fusions and Chromosomal Rearrangements

Journal article

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Inverted DNA Repeats Channel Repair of Distant Double-Strand Breaks into Chromatid Fusions and Chromosomal Rearrangements

Kelly VanHulle, Francene J Lemoine, Vidhya Narayanan, Brandon Downing, Krista Hull, Christy McCullough, Melissa Bellinger, Kirill Lobachev, Thomas D Petes and Anna Malkova

Molecular and cellular biology, Vol.27(7), pp.2601-2614

04/2007

DOI: 10.1128/MCB.01740-06

PMCID: PMC1899885

PMID: 17242181

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https://www.ncbi.nlm.nih.gov/pmc/articles/1899885View

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Abstract

Inverted DNA repeats are known to cause genomic instabilities. Here we demonstrate that double-strand DNA breaks (DSBs) introduced a large distance from inverted repeats in the yeast ( Saccharomyces cerevisiae ) chromosome lead to a burst of genomic instability. Inverted repeats located as far as 21 kb from each other caused chromosome rearrangements in response to a single DSB. We demonstrate that the DSB initiates a pairing interaction between inverted repeats, resulting in the formation of large dicentric inverted dimers. Furthermore, we observed that propagation of cells containing inverted dimers led to gross chromosomal rearrangements, including translocations, truncations, and amplifications. Finally, our data suggest that break-induced replication is responsible for the formation of translocations resulting from anaphase breakage of inverted dimers. We propose a model explaining the formation of inverted dicentric dimers by intermolecular single-strand annealing (SSA) between inverted DNA repeats. According to this model, anaphase breakage of inverted dicentric dimers leads to gross chromosomal rearrangements (GCR). This “SSA-GCR” pathway is likely to be important in the repair of isochromatid breaks resulting from collapsed replication forks, certain types of radiation, or telomere aberrations that mimic isochromatid breaks.

Details

Title: Subtitle: Inverted DNA Repeats Channel Repair of Distant Double-Strand Breaks into Chromatid Fusions and Chromosomal Rearrangements
Creators: Kelly VanHulle - Department of Biology, School of Science, IUPUI, Indianapolis, Indiana 46202, Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, North Carolina 27710, School of Biology, Georgia Institute of Technology, Atlanta, Georgia 30332
Francene J Lemoine - Department of Biology, School of Science, IUPUI, Indianapolis, Indiana 46202, Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, North Carolina 27710, School of Biology, Georgia Institute of Technology, Atlanta, Georgia 30332
Vidhya Narayanan - Department of Biology, School of Science, IUPUI, Indianapolis, Indiana 46202, Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, North Carolina 27710, School of Biology, Georgia Institute of Technology, Atlanta, Georgia 30332
Brandon Downing - Department of Biology, School of Science, IUPUI, Indianapolis, Indiana 46202, Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, North Carolina 27710, School of Biology, Georgia Institute of Technology, Atlanta, Georgia 30332
Krista Hull - Department of Biology, School of Science, IUPUI, Indianapolis, Indiana 46202, Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, North Carolina 27710, School of Biology, Georgia Institute of Technology, Atlanta, Georgia 30332
Christy McCullough - Department of Biology, School of Science, IUPUI, Indianapolis, Indiana 46202, Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, North Carolina 27710, School of Biology, Georgia Institute of Technology, Atlanta, Georgia 30332
Melissa Bellinger - Department of Biology, School of Science, IUPUI, Indianapolis, Indiana 46202, Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, North Carolina 27710, School of Biology, Georgia Institute of Technology, Atlanta, Georgia 30332
Kirill Lobachev - Department of Biology, School of Science, IUPUI, Indianapolis, Indiana 46202, Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, North Carolina 27710, School of Biology, Georgia Institute of Technology, Atlanta, Georgia 30332
Thomas D Petes - Department of Biology, School of Science, IUPUI, Indianapolis, Indiana 46202, Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, North Carolina 27710, School of Biology, Georgia Institute of Technology, Atlanta, Georgia 30332
Anna Malkova - Department of Biology, School of Science, IUPUI, Indianapolis, Indiana 46202, Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, North Carolina 27710, School of Biology, Georgia Institute of Technology, Atlanta, Georgia 30332
Resource Type: Journal article
Publication Details: Molecular and cellular biology, Vol.27(7), pp.2601-2614
DOI: 10.1128/MCB.01740-06
PMID: 17242181
PMCID: PMC1899885
NLM abbreviation: Mol Cell Biol
ISSN: 0270-7306
eISSN: 1098-5549
Publisher: American Society for Microbiology
Language: English
Date published: 04/2007
Academic Unit: Biology
Record Identifier: 9984217538802771

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