Genomes encode all RNAs required for life. For this simple reason the genome's stability is a prerequisite for maintaining the fitness of the cell, the organism and its progeny. Paradoxically, any enzymatic transaction at the DNA, including transcription itself, entails the risk of local destabilization of the DNA helix, thereby threatening genomic integrity. Particularly where transcription and replication meet, the genome may be at an increased risk of nucleotide substitution mutations, deletions or rearrangements. This Extra-view sketches our understanding of the different threats that transcription imposes on genome stability. We will focus on recent work highlighting the role of DNA damage in transcription-associated mutagenesis (TAM) in mammalian cells. Furthermore we discuss the possible implications of TAM for human fitness and disease with an emphasis on carcinogenesis. In addition, we propose an updated nomenclature for the mechanistically different forms of TAM.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.4161/cc.9.12.11987 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Viroporin activity is necessary for intercellular calcium signals that contribute to viral pathogenesis.
Sci Adv
January 2025
Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.
Viruses engage in a variety of processes to subvert host defenses and create an environment amenable to replication. Here, using rotavirus as a prototype, we show that calcium conductance out of the endoplasmic reticulum by the virus encoded ion channel, , induces intercellular calcium waves that extend beyond the infected cell and contribute to pathogenesis. Viruses that lack the ability to induce this signaling show diminished viral shedding and attenuated disease in a mouse model of rotavirus diarrhea.
View Article and Find Full Text PDFReduction of elevated Gli3 does not alter the progression of autosomal recessive polycystic kidney disease.
Physiol Rep
January 2025
Developmental Biology and Cancer Research and Teaching Department, University College London, Great Ormond Street Institute of Child Health, London, UK.
Polycystic kidney diseases (PKD) are genetic disorders which disrupt kidney architecture and function. Autosomal recessive PKD (ARPKD) is a rare form of PKD, caused by mutations in PKHD1, and clinically more severe than the more common autosomal dominant PKD (ADPKD). Prior studies have implicated Hedgehog (Hh) signaling in ADPKD, with increased levels of Hh components in experimental ADPKD and reduced cystogenesis following pharmacological Hh inhibition.
View Article and Find Full Text PDFBEND6 promotes RNA viruses' replication by inhibiting innate immune responses.
Sci China Life Sci
January 2025
National Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, China.
Innate immunity serves as a crucial defense mechanism against invading pathogens, yet its negative regulatory network remains under explored. In this study, we identify BEN domain-containing protein 6 (BEND6) as a novel negative regulator of innate immunity through a genome-scale CRISPR knockout screen for host factors essential for viral replication. We show that BEND6 exhibits characteristics of an interferon-stimulated gene (ISG), with its mRNA and protein levels upregulated by RNA virus-induced IFN-β.
View Article and Find Full Text PDFNanopore sequencing reveals that DNA replication compartmentalisation dictates genome stability and instability in Trypanosoma brucei.
Nat Commun
January 2025
University of Glasgow Centre for Parasitology, The Wellcome Centre for Integrative Parasitology, University of Glasgow, School of Infection and Immunity, Sir Graeme Davies Building, 120 University Place, Glasgow, G12 8TA, United Kingdom.
The Trypanosoma brucei genome is structurally complex. Eleven megabase-sized chromosomes each comprise a transcribed core flanked by silent subtelomeres, housing thousands of Variant Surface Glycoprotein (VSG) genes. Additionally, hundreds of sub-megabase chromosomes contain 177 bp repeats of unknown function, and VSG transcription sites localise to many telomeres.
View Article and Find Full Text PDFThe hidden weavers: A review of DNA/RNA R-loops in stem cell biology and therapeutic potential.
Int J Biol Macromol
January 2025
Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou 510280, Guangdong, China. Electronic address:
R-loops, three-stranded nucleic acid structures composed of RNA-DNA hybrids, are increasingly recognized as central regulators of genomic stability and transcription. These structures play critical roles across various cellular processes, including DNA replication, repair, and gene regulation, with significant implications for stem cell biology and disease pathogenesis. This review comprehensively explores the molecular underpinnings of R-loop formation, emphasizing the dual nature of R-loops in both facilitating normal cellular functions and contributing to genomic instability.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!