Analysis of the functional domains of the mismatch repair homologue Msh1p and its role in mitochondrial genome maintenance.

Abstract:

:Mitochondrial DNA (mtDNA) repair occurs in all eukaryotic organisms and is essential for the maintenance of mitochondrial function. Evidence from both humans and yeast suggests that mismatch repair is one of the pathways that functions in overall mtDNA stability. In the mitochondria of the yeast Saccharomyces cerevisiae, the presence of a homologue to the bacterial MutS mismatch repair protein, MSH1, has long been known to be essential for mitochondrial function. The mechanisms for which it is essential are unclear, however. Here, we analyze the effects of two point mutations, msh1-F105A and msh1-G776D, both predicted to be defective in mismatch repair; and we show that they are both able to maintain partial mitochondrial function. Moreover, there are significant differences in the severity of mitochondrial disruption between the two mutants that suggest multiple roles for Msh1p in addition to mismatch repair. Our overall findings suggest that these additional predicted functions of Msh1p, including recombination surveillance and heteroduplex rejection, may be primarily responsible for its essential role in mtDNA stability.

journal_name

Curr Genet

journal_title

Current genetics

authors

Mookerjee SA,Lyon HD,Sia EA

doi

10.1007/s00294-004-0537-1

subject

Has Abstract

pub_date

2005-02-01 00:00:00

pages

84-99

issue

2

eissn

0172-8083

issn

1432-0983

journal_volume

47

pub_type

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