DNA replication restart, the essential process that reinitiates prematurely terminated genome replication reactions, relies on exquisitely specific recognition of abandoned DNA replication-fork structures. The PriA DNA helicase mediates this process in bacteria through mechanisms that remain poorly defined. We report the crystal structure of a PriA/replication-fork complex, which resolves leading-strand duplex DNA bound to the protein. Interaction with PriA unpairs one end of the DNA and sequesters the 3'-most nucleotide from the nascent leading strand into a conserved protein pocket. Cross-linking studies reveal a surface on the winged-helix domain of PriA that binds to parental duplex DNA. Deleting the winged-helix domain alters PriA's structure-specific DNA unwinding properties and impairs its activity in vivo. Our observations lead to a model in which coordinated parental-, leading-, and lagging-strand DNA binding provide PriA with the structural specificity needed to act on abandoned DNA replication forks.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6166810 | PMC |
| http://dx.doi.org/10.1073/pnas.1809842115 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Mitochondrial epigenetics brings new perspectives on doubly uniparental inheritance in bivalves.
Sci Rep
December 2024
Department of Biological Sciences, Université de Montréal, Montréal, QC, Canada.
Mitochondrial epigenetics, particularly mtDNA methylation, is a flourishing field of research. MtDNA methylation appears to play multiple roles, including regulating mitochondrial transcription, cell metabolism and mitochondrial inheritance. In animals, bivalves with doubly uniparental inheritance (DUI) of mitochondria are the exception to the rule of maternal mitochondrial inheritance since DUI also involve a paternal mtDNA transmitted from the father to sons.
View Article and Find Full Text PDFGenotoxic effects of NDMA-contaminated ranitidine on Allium cepa cells and unveiling carcinogenic mechanisms via DFT and molecular dynamics simulation study.
Sci Rep
December 2024
Department of Genetic Engineering and Biotechnology, University of Rajshahi, Rajshahi, 6205, Bangladesh.
This study investigated the potential genotoxic and carcinogenic effects of N-nitrosodimethylamine (NDMA), a hazardous compound found in ranitidine formulations that are used to treat excessive stomach acid. The study first examined the effects of NDMA-contaminated ranitidine formulation on Allium cepa root growth and mitotic activity. The results demonstrated dose-dependent decreases in both root growth and mitotic index indicating genotoxicity and cell division disruption.
View Article and Find Full Text PDFTranscriptomic and genetic profiling in a spontaneous non-human primate model of hypertrophic cardiomyopathy and sudden cardiac death.
Sci Rep
December 2024
Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, 1060 William Moore Dr, Raleigh, NC, 27607, USA.
Hypertrophic cardiomyopathy (HCM) afflicts humans, cats, pigs, and rhesus macaques. Disease sequelae include congestive heart failure, thromboembolism, and sudden cardiac death (SCD). Sarcomeric mutations explain some human and cat cases, however, the molecular basis in rhesus macaques remains unknown.
View Article and Find Full Text PDFEthnogenetic analysis reveals the Bronze Age genetic affiliation of Yashkuns with West Eurasians.
Sci Rep
December 2024
Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, 11451, Saudi Arabia.
Focusing on the Yashkun population of Gilgit-Baltistan, an administrative territory in northern Pakistan, our study investigated mtDNA haplotypes as indicators of ancient gene flow and genetic diversity. Genomic DNA was extracted and evaluated for quality using agarose gel electrophoresis. The complete control region of mtDNA (nt 16024-576) was amplified via PCR, and sequencing was performed using the Big Dye Terminator Kit on an Applied Biosystems Genetic Analyzer.
View Article and Find Full Text PDFIdentification and validation of KIF20A for predicting prognosis and treatment outcomes in patients with breast cancer.
Sci Rep
December 2024
Department of Breast Surgery, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China.
Breast cancer is a leading cause of cancer-related deaths among women globally. It is imperative to explore novel biomarkers to predict breast cancer treatment response as well as progression. Here, we collected six breast cancer samples and paired normal tissues for high-throughput sequencing.
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!