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Copy-choice recombination during mitochondrial L-strand synthesis causes DNA deletions.

Abstract：

:Mitochondrial DNA (mtDNA) deletions are associated with mitochondrial disease, and also accumulate during normal human ageing. The mechanisms underlying mtDNA deletions remain unknown although several models have been proposed. Here we use deep sequencing to characterize abundant mtDNA deletions in patients with mutations in mitochondrial DNA replication factors, and show that these have distinct directionality and repeat characteristics. Furthermore, we recreate the deletion formation process in vitro using only purified mitochondrial proteins and defined DNA templates. Based on our in vivo and in vitro findings, we conclude that mtDNA deletion formation involves copy-choice recombination during replication of the mtDNA light strand.

journal_name

Nat Commun

journal_title

Nature communications

authors

Persson Ö,Muthukumar Y,Basu S,Jenninger L,Uhler JP,Berglund AK,McFarland R,Taylor RW,Gustafsson CM,Larsson E,Falkenberg M

doi

10.1038/s41467-019-08673-5

subject

Has Abstract

pub_date

2019-02-15 00:00:00

pages

759

issue

1

issn

2041-1723

pii

10.1038/s41467-019-08673-5

journal_volume

10

pub_type

杂志文章

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