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Biochemistry (Moscow)

, Volume 83, Issue 3, pp 233–249 | Cite as

Mechanisms of Mitochondrial DNA Repair in Mammals

  • L. A. ZinovkinaEmail author
Review

Abstract

Accumulation of mutations in mitochondrial DNA leads to the development of severe, currently untreatable diseases. The contribution of these mutations to aging and progress of neurodegenerative diseases is actively studied. Elucidation of DNA repair mechanisms in mitochondria is necessary for both developing approaches to the therapy of diseases caused by mitochondrial mutations and understanding specific features of mitochondrial genome functioning. Mitochondrial DNA repair systems have become a subject of extensive studies only in the last decade due to development of molecular biology methods. DNA repair systems of mammalian mitochondria appear to be more diverse and effective than it had been thought earlier. Even now, one may speak about the existence of mitochondrial mechanisms for the repair of single–and double–stranded DNA lesions. Homologous recombination also takes place in mammalian mitochondria, although its functional significance and molecular mechanisms remain obscure. In this review, I describe DNA repair systems in mammalian mitochondria, such as base excision repair (BER) and microhomology–mediated end joining (MMEJ) and discuss a possibility of existence of mitochondrial DNA repair mechanisms otherwise typical for the nuclear DNA, e.g., nucleotide excision repair (NER), mismatch repair (MMR), homologous recombination, and classical non–homologous end joining (NHEJ). I also present data on the mechanisms for coordination of the nuclear and mitochondrial DNA repair systems that have been actively studied recently.

Keywords

mitochondria mitochondrial DNA mutations DNA repair BER MMEJ homologous recombination PARP1 

Abbreviations

APTX

aprataxin

BER

base excision repair

CSA

Cockayne syndrome protein A

CSB

Cockayne syndrome protein B

ETC

electron transport chain

EXOG1

exo/endonuclease G

FEN1

flap structure–specific endonuclease 1

LP BER

long patch base excision repair

MMEJ

microhomology–mediated end joining

MMR

mismatch repair

mtDNA

mitochondrial DNA

NER

nucleotide excision repair

NHEJ

non–homologous end joining

OGG1

8–oxoguanine–DNA–glycosylase

8–oxo–dG

8–hydroxy–2′–deoxyguanosine

PAR

poly(ADP–ribose)

PARP1

poly(ADP–ribose) polymerase

POLRMT

mitochondrial RNA polymerase

rDNA

ribosomal DNA

ROS

reactive oxygen species

SP BER

short patch base excision repair

SSB

single–strand binding protein

TDP1

tyrosyl–DNA phosphodiesterase 1

TFAM

transcriptional factor A of mitochondria

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© Pleiades Publishing, Ltd. 2018

Authors and Affiliations

  1. 1.Lomonosov Moscow State UniversityFaculty of Bioengineering and BioinformaticsMoscowRussia

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