scholarly journals Mitochondrial Genome Maintenance: Damage and Repair Pathways

Author(s):  
Ulises Omar García-Lepe ◽  
Rosa Ma Bermúdez-Cruz
Author(s):  
Matthew Glover Addo ◽  
Raynald Cossard ◽  
Damien Pichard ◽  
Kwasi Obiri-Danso ◽  
Agnès Rötig ◽  
...  

Genetics ◽  
2012 ◽  
Vol 190 (3) ◽  
pp. 951-964 ◽  
Author(s):  
Lidza Kalifa ◽  
Daniel F. Quintana ◽  
Laura K. Schiraldi ◽  
Naina Phadnis ◽  
Garry L. Coles ◽  
...  

2017 ◽  
Vol 38 (3) ◽  
Author(s):  
Anup Mishra ◽  
Sneha Saxena ◽  
Anjali Kaushal ◽  
Ganesh Nagaraju

ABSTRACT Mechanisms underlying mitochondrial genome maintenance have recently gained wide attention, as mutations in mitochondrial DNA (mtDNA) lead to inherited muscular and neurological diseases, which are linked to aging and cancer. It was previously reported that human RAD51, RAD51C, and XRCC3 localize to mitochondria upon oxidative stress and are required for the maintenance of mtDNA stability. Since RAD51 and RAD51 paralogs are spontaneously imported into mitochondria, their precise role in mtDNA maintenance under unperturbed conditions remains elusive. Here, we show that RAD51C/XRCC3 is an additional component of the mitochondrial nucleoid having nucleus-independent roles in mtDNA maintenance. RAD51C/XRCC3 localizes to the mtDNA regulatory regions in the D-loop along with the mitochondrial polymerase POLG, and this recruitment is dependent upon Twinkle helicase. Moreover, upon replication stress, RAD51C and XRCC3 are further enriched at the mtDNA mutation hot spot region D310. Notably, the absence of RAD51C/XRCC3 affects the stability of POLG on mtDNA. As a consequence, RAD51C/XRCC3-deficient cells exhibit reduced mtDNA synthesis and increased lesions in the mitochondrial genome, leading to overall unhealthy mitochondria. Together, these findings lead to the proposal of a mechanism for a direct role of RAD51C/XRCC3 in maintaining mtDNA integrity under replication stress conditions.


eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Dorine Jeanne Mariëtte du Mee ◽  
Maxim Ivanov ◽  
Joseph Paul Parker ◽  
Stephen Buratowski ◽  
Sebastian Marquardt

Most DNA in the genomes of higher organisms does not code for proteins. RNA Polymerase II (Pol II) transcribes non-coding DNA into long non-coding RNAs (lncRNAs), but biological roles of lncRNA are unclear. We find that mutations in the yeast lncRNA CUT60 result in poor growth. Defective termination of CUT60 transcription causes read-through transcription across the ATP16 gene promoter. Read-through transcription localizes chromatin signatures associated with Pol II elongation to the ATP16 promoter. The act of Pol II elongation across this promoter represses functional ATP16 expression by a Transcriptional Interference (TI) mechanism. Atp16p function in the mitochondrial ATP-synthase complex promotes mitochondrial DNA stability. ATP16 repression by TI through inefficient termination of CUT60 therefore triggers mitochondrial genome loss. Our results expand the functional and mechanistic implications of non-coding DNA in eukaryotes by highlighting termination of nuclear lncRNA transcription as mechanism to stabilize an organellar genome.


Author(s):  
Kalyan Mahapatra ◽  
Samrat Banerjee ◽  
Sayanti De ◽  
Mehali Mitra ◽  
Pinaki Roy ◽  
...  

Besides the nuclear genome, plants possess two small extra chromosomal genomes in mitochondria and chloroplast, respectively, which contribute a small fraction of the organelles’ proteome. Both mitochondrial and chloroplast DNA have originated endosymbiotically and most of their prokaryotic genes were either lost or transferred to the nuclear genome through endosymbiotic gene transfer during the course of evolution. Due to their immobile nature, plant nuclear and organellar genomes face continuous threat from diverse exogenous agents as well as some reactive by-products or intermediates released from various endogenous metabolic pathways. These factors eventually affect the overall plant growth and development and finally productivity. The detailed mechanism of DNA damage response and repair following accumulation of various forms of DNA lesions, including single and double-strand breaks (SSBs and DSBs) have been well documented for the nuclear genome and now it has been extended to the organelles also. Recently, it has been shown that both mitochondria and chloroplast possess a counterpart of most of the nuclear DNA damage repair pathways and share remarkable similarities with different damage repair proteins present in the nucleus. Among various repair pathways, homologous recombination (HR) is crucial for the repair as well as the evolution of organellar genomes. Along with the repair pathways, various other factors, such as the MSH1 and WHIRLY family proteins, WHY1, WHY2, and WHY3 are also known to be involved in maintaining low mutation rates and structural integrity of mitochondrial and chloroplast genome. SOG1, the central regulator in DNA damage response in plants, has also been found to mediate endoreduplication and cell-cycle progression through chloroplast to nucleus retrograde signaling in response to chloroplast genome instability. Various proteins associated with the maintenance of genome stability are targeted to both nuclear and organellar compartments, establishing communication between organelles as well as organelles and nucleus. Therefore, understanding the mechanism of DNA damage repair and inter compartmental crosstalk mechanism in various sub-cellular organelles following induction of DNA damage and identification of key components of such signaling cascades may eventually be translated into strategies for crop improvement under abiotic and genotoxic stress conditions. This review mainly highlights the current understanding as well as the importance of different aspects of organelle genome maintenance mechanisms in higher plants.


2011 ◽  
Vol 22 (12) ◽  
pp. 1955-1959 ◽  
Author(s):  
Matthew L. Bochman ◽  
Colleen P. Judge ◽  
Virginia A. Zakian

Pif1 family helicases, which are found in nearly all eukaryotes, have important roles in both nuclear and mitochondrial genome maintenance. Recently, the increasing availability of genome sequences has revealed that Pif1 helicases are also widely found in diverse prokaryotes, but it is currently unknown what physiological function(s) prokaryotic Pif1 helicases might perform. This Perspective aims to briefly introduce the reader to the well-studied eukaryotic Pif1 family helicases and speculate on what roles such enzymes may play in bacteria. On the basis of our hypotheses, we predict that Pif1 family helicases are important for resolving common issues that arise during DNA replication, recombination, and repair rather than functioning in a eukaryotic-specific manner.


2010 ◽  
Vol 21 (1) ◽  
pp. 12-20 ◽  
Author(s):  
G. Elachouri ◽  
S. Vidoni ◽  
C. Zanna ◽  
A. Pattyn ◽  
H. Boukhaddaoui ◽  
...  

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