Analysis of Repeat-Mediated Deletions in the Mitochondrial Genome of Saccharomyces cerevisiae

Mitochondrial DNA deletions and point mutations accumulate in an age-dependent manner in mammals. The mitochondrial genome in aging humans often displays a 4977-bp deletion flanked by short direct repeats. Additionally, direct repeats flank two-thirds of the reported mitochondrial DNA deletions. The...

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Bibliographic Details
Published in:Genetics (Austin) 2005-12, Vol.171 (4), p.1549-1559
Main Authors: Phadnis, Naina, Sia, Rey A, Sia, Elaine A
Format: Article
Language:English
Subjects:
Blotting, Southern
Deoxyribonucleic acid
DNA
DNA, Mitochondrial - genetics
Gene Deletion
Genes
Genetics
Investigations
Mitochondrial DNA
Models, Genetic
Mutation
Mutation - genetics
Polymerase Chain Reaction
Proteins
Repetitive Sequences, Nucleic Acid - genetics
Saccharomyces cerevisiae
Saccharomyces cerevisiae - genetics
Yeast
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Summary:Mitochondrial DNA deletions and point mutations accumulate in an age-dependent manner in mammals. The mitochondrial genome in aging humans often displays a 4977-bp deletion flanked by short direct repeats. Additionally, direct repeats flank two-thirds of the reported mitochondrial DNA deletions. The mechanism by which these deletions arise is unknown, but direct-repeat-mediated deletions involving polymerase slippage, homologous recombination, and nonhomologous end joining have been proposed. We have developed a genetic reporter to measure the rate at which direct-repeat-mediated deletions arise in the mitochondrial genome of Saccharomyces cerevisiae. Here we analyze the effect of repeat size and heterology between repeats on the rate of deletions. We find that the dependence on homology for repeat-mediated deletions is linear down to 33 bp. Heterology between repeats does not affect the deletion rate substantially. Analysis of recombination products suggests that the deletions are produced by at least two different pathways, one that generates only deletions and one that appears to generate both deletions and reciprocal products of recombination. We discuss how this reporter may be used to identify the proteins in yeast that have an impact on the generation of direct-repeat-mediated deletions.
ISSN:0016-6731
1943-2631
1943-2631
DOI:10.1534/genetics.105.047092