Saccharomyces cerevisiae Mhr1 can bind Xho I-induced mitochondrial DNA double-strand breaks in vivo

Abstract

Mitochondrial DNA (mtDNA) double-strand break (DSB) repair is essential for maintaining mtDNA integrity, but little is known about the proteins involved in mtDNA DSB repair. Here, we utilize Saccharomyces cerevisiae as a eukaryotic model to identify proteins involved in mtDNA DSB repair. We show that Mhr1, a protein known to possess homologous DNA pairing activity in vitro, binds to mtDNA DSBs in vivo, indicating its involvement in mtDNA DSB repair. Our data also indicate that Yku80, a protein previously implicated in mtDNA DSB repair, does not compete with Mhr1 for binding to mtDNA DSBs. In fact, C-terminally tagged Yku80 could not be detected in yeast mitochondrial extracts. Therefore, we conclude that Mhr1, but not Yku80, is a potential mtDNA DSB repair factor in yeast.

Rolling-Circle Replication in Mitochondrial DNA Inheritance: Scientific Evidence and Significance from Yeast to Human Cells

“…In contrast to Mhr1, overproduction of the Abf2 leads to mtDNA instability [89]. Mhr1 localizes near DSB sites in mtDNA [68], and exogenous introduction of Mhr1 promotes mtDNA recombination, thereby preventing mtDNA deletion-attributed deficiency in respiratory function [91]. This is consistent with the conclusion that Mhr1 plays a pivotal role in mtDNA maintenance [94].…”

“…In the rolling-circle mode, the mitochondrial recombinase Mhr1 mediates homologous DNA pairing to initiate the rolling-circle mtDNA replication (Figure 1). In addition, Mhr1 can bind mtDNA double-strand breaks (DSBs) and mediate homologous DNA recombination, the predominant pathway for repair of mtDNA DSBs [67,68]. Several factors that collaborate with Mhr1 have been identified.…”

SUMOylation of yeast Pso2 enhances its translocation and accumulation in the mitochondria and suppresses methyl methanesulfonate‐induced mitochondrial DNA damage

“…Among the multiple pathways of DNA repair, studies on different mammalian cells have documented the presence of DNA repair factors involved in base excision repair (BER), direct reversal, mismatch repair and double-strand break repair in the mitochondria (Rong et al, 2021;Saki & Prakash, 2017). Further, previous studies have also demonstrated the presence of DNA repair enzymes involved in BER pathway, including DNA glycosylases Ntg1 and Ntg2 (You et al, 1999), OGG1 (Singh et al, 2001), APN1 endonuclease (Acevedo-Torres et al, 2009) and DSB repair factors, such as Mhr1, Yku80 and members of Rad50 epistasis group in S. cerevisiae mitochondria (Kalifa et al, 2012;Prasai et al, 2018;Ricchetti et al, 1999;Stein et al, 2015). However, certain repair pathways, such as mismatch repair and NER seem to be absent in the S. cerevisiae mitochondria (Alencar et al, 2019).…”

Transcriptomic analysis reveals hub genes and pathways in response to acetic acid stress in Kluyveromyces marxianus during high-temperature ethanol fermentation

“…These genes participate in the biogenesis of mitochondrial ribosomes and play an active role in mitochondrial translation. The gene MHR1 is involved in repairing mitochondrial DNA double-strand breaks and encodes mitochondrial homologous recombination protein 1, which is crucial for maintaining mitochondrial function and repairing mitochondrial DNA lesions (Prasai et al 2018 ). PET122 is necessary for the translation of cytochrome c oxidase subunit III (Ohmen et al 1988 ), a component of the electron transport chain that is essential for ATP production.…”