DNA-RNA hybrids play a physiological role in cellular processes, but often, they represent non-scheduled co-transcriptional structures with a negative impact on transcription, replication and DNA repair. Accumulating evidence suggests that they constitute a source of replication stress, DNA breaks and genome instability. Reciprocally, DNA breaks facilitate DNA-RNA hybrid formation by releasing the double helix torsional conformation. Cells avoid DNA-RNA accumulation by either preventing or removing hybrids directly or by DNA repair-coupled mechanisms. Given the R-loop impact on chromatin and genome organization and its potential relation with genetic diseases, we review R-loop homeostasis as well as their physiological and pathological roles.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.cell.2019.08.055 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Malate initiates a proton-sensing pathway essential for pH regulation of inflammation.
Signal Transduct Target Ther
December 2024
Department of Orthopedic Surgery/Sports Medicine Center, Southwest Hospital, Army Medical University, Chongqing, 400038, China.
Metabolites can double as a signaling modality that initiates physiological adaptations. Metabolism, a chemical language encoding biological information, has been recognized as a powerful principle directing inflammatory responses. Cytosolic pH is a regulator of inflammatory response in macrophages.
View Article and Find Full Text PDFMolecular Mechanisms Underlying the Loop-Closing Dynamics of β-1,4 Galactosyltransferase 1.
J Chem Inf Model
December 2024
Xuzhou College of Industrial Technology, Xuzhou 221140, Jiangsu Province, China.
The β-1,4 galactosylation catalyzed by β-1,4 galactosyltransferases (β4Gal-Ts) is not only closely associated with diverse physiological and pathological processes in humans but also widely applied in the -glycan modification of protein glycoengineering. The loop-closing process of β4Gal-Ts is an essential intermediate step intervening in the binding events of donor substrate (UDP-Gal/Mn) and acceptor substrate during its catalytic cycle, with a significant impact on the galactosylation activities. However, the molecular mechanisms in regulating loop-closing dynamics are not entirely clear.
View Article and Find Full Text PDFEpithelial Polarity Loss and Multilayer Formation: Insights Into Tumor Growth and Regulatory Mechanisms.
Bioessays
December 2024
Department of Biochemistry and Molecular Biology, Louisiana Cancer Research Center, Tulane University School of Medicine, New Orleans, Louisiana, USA.
Epithelial tissues serve as critical barriers in metazoan organisms, maintaining structural integrity and facilitating essential physiological functions. Epithelial cell polarity regulates mechanical properties, signaling, and transport, ensuring tissue organization and homeostasis. However, the barrier function is challenged by cell turnover during development and maintenance.
View Article and Find Full Text PDFNon-APOE variants predominately expressed in smooth muscle cells contribute to the influence of Alzheimer's disease genetic risk on white matter hyperintensities.
Alzheimers Dement
December 2024
Department of Psychology, University of Bath, Bath, UK.
Introduction: White matter hyperintensity volumes (WMHVs) are disproportionally prevalent in individuals with Alzheimer's disease (AD), potentially reflecting neurovascular injury. We quantify the association between AD polygenic risk score (AD-PRS) and WMHV, exploring single-nucleotide polymorphisms (SNPs) that are proximal to genes overexpressed in cerebrovascular cell species.
Methods: In a UK-Biobank sub-sample (mean age = 64, range = 45-81 years), we associate WMHV with (1) AD-PRS estimated via SNPs across the genome (minus apolipoprotein E [APOE] locus) and (2) AD-PRS estimated with SNPs proximal to specific genes that are overexpressed in cerebrovascular cell species.
miR-210 loss leads to widespread phenotypic and gene expression changes in human 293T cells.
Front Genet
December 2024
Department of Zoology, College of Life Sciences, Nanjing Agricultural University, Nanjing, Jiangsu, China.
Introduction: Hypoxia responses are critical for myriad physiological and pathological processes, such as development, tissue repair, would healing, and tumorigenesis. microRNAs (miRNAs) are a class of small non-coding RNAs that exert their functions by inhibiting the expression of their target genes, and miR-210 is the miRNA universally and most conspicuously upregulated by hypoxia in mammalian systems. For its relationship to hypoxia, miR-210 has been studied extensively, yet no consensus exists on the roles and mechanisms of miR-210 in human physiological processes or diseases, and we know little about genuine miR-210 target genes in humans.
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!