REC drives recombination to repair double-strand breaks in animal mtDNA

Anna Klucnika, Peiqiang Mu, Jan Jezek, Matthew McCormack, Ying Di, Charles R. Bradshaw, Hansong Ma

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Abstract

Mechanisms that safeguard mitochondrial DNA (mtDNA) limit the accumulation of mutations linked to mitochondrial and age-related diseases. Yet, pathways that repair double-strand breaks (DSBs) in animal mitochondria are poorly understood. By performing a candidate screen for mtDNA repair proteins, we identify that REC—an MCM helicase that drives meiotic recombination in the nucleus—also localizes to mitochondria in Drosophila. We show that REC repairs mtDNA DSBs by homologous recombination in somatic and germline tissues. Moreover, REC prevents age-associated mtDNA mutations. We further show that MCM8, the human ortholog of REC, also localizes to mitochondria and limits the accumulation of mtDNA mutations. This study provides mechanistic insight into animal mtDNA recombination and demonstrates its importance in safeguarding mtDNA during ageing and evolution.
Original languageEnglish
Article numbere202201137
Number of pages19
JournalJournal of Cell Biology
Volume222
Issue number1
Early online date10 Nov 2022
DOIs
Publication statusPublished - 2 Jan 2023

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