Mitochondrial DNA topology is critical for mitochondrial genome maintenance and the regulation of gene expression

Mitochondrion ◽  
2015 ◽  
Vol 24 ◽  
pp. S28
Author(s):  
James Byrnes ◽  
Neal Sondheimer
Keyword(s):  
Gene Expression ◽  
Mitochondrial Dna ◽  
Mitochondrial Genome ◽  
Regulation Of Gene Expression ◽  
Dna Topology ◽  
Genome Maintenance

scholarly journals RAD51C/XRCC3 Facilitates Mitochondrial DNA Replication and Maintains Integrity of the Mitochondrial Genome

2017 ◽  
Vol 38 (3) ◽  
Author(s):  
Anup Mishra ◽  
Sneha Saxena ◽  
Anjali Kaushal ◽  
Ganesh Nagaraju
Keyword(s):  
Mitochondrial Dna ◽  
Mitochondrial Genome ◽  
Hot Spot ◽  
Neurological Diseases ◽  
Replication Stress ◽  
Genome Maintenance ◽  
Mtdna Mutation ◽  
Direct Role ◽  
D Loop ◽  
The Stability

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.

Improved detection of mitochondrial DNA instability in mitochondrial genome maintenance disorders

2021 ◽  
Author(s):  
Celine Bris ◽  
David Goudenège ◽  
Valerie Desquiret-Dumas ◽  
Naig Gueguen ◽  
Sylvie Bannwarth ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Mitochondrial Genome ◽  
Genome Maintenance ◽  
Dna Instability ◽  
Mitochondrial Dna Instability

scholarly journals New Insights into Structural and Functional Roles of Indole-3-acetic acid (IAA): Changes in DNA Topology and Gene Expression in Bacteria

Biomolecules ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. 522 ◽  
Author(s):  
Defez ◽  
Valenti ◽  
Andreozzi ◽  
Romano ◽  
Ciaramella ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acetic Acid ◽  
Conformational Changes ◽  
Regulation Of Gene Expression ◽  
Dna Supercoiling ◽  
Dna Topology ◽  
In Vitro Assays ◽  
Bacterial Cells ◽  
Indole 3 Acetic Acid

: Indole-3-acetic acid (IAA) is a major plant hormone that affects many cellular processes in plants, bacteria, yeast, and human cells through still unknown mechanisms. In this study, we demonstrated that the IAA-treatment of two unrelated bacteria, the Ensifer meliloti 1021 and Escherichia coli, harboring two different host range plasmids, influences the supercoiled state of the two plasmid DNAs in vivo. Results obtained from in vitro assays show that IAA interacts with DNA, leading to DNA conformational changes commonly induced by intercalating agents. We provide evidence that IAA inhibits the activity of the type IA topoisomerase, which regulates the DNA topological state in bacteria, through the relaxation of the negative supercoiled DNA. In addition, we demonstrate that the treatment of E. meliloti cells with IAA induces the expression of some genes, including the ones related to nitrogen fixation. In contrast, these genes were significantly repressed by the treatment with novobiocin, which reduces the DNA supercoiling in bacterial cells. Taking into account the overall results reported, we hypothesize that the IAA action and the DNA structure/function might be correlated and involved in the regulation of gene expression. This work points out that checking whether IAA influences the DNA topology under physiological conditions could be a useful strategy to clarify the mechanism of action of this hormone, not only in plants but also in other unrelated organisms.

Linking transcription, RNA polymerase II elongation and alternative splicing

2020 ◽  
Vol 477 (16) ◽  
pp. 3091-3104 ◽  
Author(s):  
Luciana E. Giono ◽  
Alberto R. Kornblihtt
Keyword(s):  
Gene Expression ◽  
Alternative Splicing ◽  
Rna Polymerase Ii ◽  
Environmental Changes ◽  
Transcription Elongation ◽  
Single Gene ◽  
Regulation Of Gene Expression ◽  
Regulation Of Transcription ◽  
Stepping Stones ◽  
Eukaryotic Transcription

Gene expression is an intricately regulated process that is at the basis of cell differentiation, the maintenance of cell identity and the cellular responses to environmental changes. Alternative splicing, the process by which multiple functionally distinct transcripts are generated from a single gene, is one of the main mechanisms that contribute to expand the coding capacity of genomes and help explain the level of complexity achieved by higher organisms. Eukaryotic transcription is subject to multiple layers of regulation both intrinsic — such as promoter structure — and dynamic, allowing the cell to respond to internal and external signals. Similarly, alternative splicing choices are affected by all of these aspects, mainly through the regulation of transcription elongation, making it a regulatory knob on a par with the regulation of gene expression levels. This review aims to recapitulate some of the history and stepping-stones that led to the paradigms held today about transcription and splicing regulation, with major focus on transcription elongation and its effect on alternative splicing.

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