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The role of 3 '-5 ' exonucleolytic proofreading and mismatch repair in yeast mitochondrial DNA error avoidance

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Vanderstraeten, S. Van Den Brûle, Sybille [UCL] Hu, JP. Foury, Françoise [UCL]

In the D171G/D2SOA mutant generated at conserved aspartate residues in the Exo1 and Exo2 sites of the 3'-5' exonuclease domain of the yeast mitochondrial DNA (mtDNA) polymerase (pol-gamma), the mitochondrial genome is unstable and the frequency of mtDNA point mutations is 1500 times higher than in the wild-type strain and 10 times higher than in single substitution mutants. The 10(4)-fold decrease in the 3'-5' exonuclease activity of the purified mtDNA polymerase is associated with mismatch extension and high rates of base misincorporation. Processivity of the purified polymerase on primed single-stranded DNA is decreased and the K-m for dNTP is increased. The sequencing of mtDNA point mutations in the wild-type strain and in proofreading and mismatch-repair deficient mutants shows that mismatch repair contributes to elimination of the transitions while exonucleolytic proofreading preferentially repairs transversions, and more specifically A to T (or T to A) transversions. However, even in the wild-type strain, A to T (or T to A) transversions are the most frequent substitutions, suggesting that they are imperfectly repaired. The combination of both mismatch repair and proofreading deficiencies elicits a mitochondrial error catastrophe. These data show that the faithful replication of yeast mtDNA requires both exonucleolytic proofreading and mismatch repair.

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès restreint
Publication date 1998
Language Anglais
Journal information "Journal of Biological Chemistry" - Vol. 273, no. 37, p. 23690-23697 (1998)
Peer reviewed yes
Publisher Amer Soc Biochemistry Molecular Biology Inc (Bethesda)
issn 0021-9258
e-issn 1083-351X
Publication status Publié
Affiliation UCL - AGRO/CABI - Département de chimie appliquée et des bio-industries
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Bibliographic reference Vanderstraeten, S. ; Van Den Brûle, Sybille ; Hu, JP. ; Foury, Françoise. The role of 3 '-5 ' exonucleolytic proofreading and mismatch repair in yeast mitochondrial DNA error avoidance. In: Journal of Biological Chemistry, Vol. 273, no. 37, p. 23690-23697 (1998)
Permanent URL http://hdl.handle.net/2078.1/45081