AI Article Synopsis

  • - The study discusses how the structure of DNA changes during replication and when proteins are removed in lab conditions, and highlights the impact of superhelical stress on the DNA during this process.
  • - Topo IV, an enzyme, plays a crucial role in relaxing supercoiled DNA ahead of replication forks, but it isn't the only player; DNA gyrase also helps in this process, suggesting a teamwork approach in vivo.
  • - Even though Topo IV isn't as effective at unlinking certain DNA structures after replication, its main function seems to be managing the linked DNA strands, which is why replication can still happen without it, but the sister DNA strands remain entangled.

Article Abstract

The topology of DNA duplexes changes during replication and also after deproteinization in vitro. Here we describe these changes and then discuss for the first time how the distribution of superhelical stress affects the DNA topology of replication intermediates, taking into account the progression of replication forks. The high processivity of Topo IV to relax the left-handed (+) supercoiling that transiently accumulates ahead of the forks is not essential, since DNA gyrase and swiveling of the forks cooperate with Topo IV to accomplish this task in vivo. We conclude that despite Topo IV has a lower processivity to unlink the right-handed (+) crossings of pre-catenanes and fully replicated catenanes, this is indeed its main role in vivo. This would explain why in the absence of Topo IV replication goes-on, but fully replicated sister duplexes remain heavily catenated.

Download full-text PDF

Source
http://dx.doi.org/10.1002/bies.202000309DOI Listing

Publication Analysis

Top Keywords

topology dna
8
replication intermediates
8
fully replicated
8
replication
5
changes topology
4
dna
4
dna replication
4
intermediates discrepancies
4
discrepancies vitro
4
vitro vivo
4

Similar Publications

Multifunctional Mycobacterial Topoisomerases with Distinctive Features.

ACS Infect Dis

January 2025

Department of Microbiology and Cell Biology, Indian Institute of Science, C.V. Raman Avenue, Bangalore 560012, India.

Tuberculosis (TB) continues to be a major cause of death worldwide despite having an effective combinatorial therapeutic regimen and vaccine. Being one of the most successful human pathogens, retains the ability to adapt to diverse intracellular and extracellular environments encountered by it during infection, persistence, and transmission. Designing and developing new therapeutic strategies to counter the emergence of multidrug-resistant and extensively drug-resistant TB remains a major task.

View Article and Find Full Text PDF

Na-concentration dependent conformational switch of oncogene RET G-quadruplex DNA in solution.

Int J Biol Macromol

January 2025

State Key Laboratory of Chemical Biology, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200032, China. Electronic address:

Proto-oncogene RET is overexpressed in many cancers, and its expression level is positively related to the size and malignancy of the tumors. Effective inhibition of its overexpression can be used to potentially treat cancers. A guanine-rich GC-boxes (I-V) sequence in its promoter region folds into noncanonical G-quadruplex (G4) DNA structures, negatively regulating its expression by interactions with small molecules.

View Article and Find Full Text PDF

DNA gyrase is a bacterial type IIA topoisomerase that can create temporary double-stranded DNA breaks to regulate DNA topology and an archetypical target of antibiotics. The widely used quinolone class of drugs use a water-metal ion bridge in interacting with the GyrA subunit of DNA gyrase. Zoliflodacin sits in the same pocket as quinolones but interacts with the GyrB subunit and also stabilizes lethal double-stranded DNA breaks.

View Article and Find Full Text PDF

DNA damage and its links to neuronal aging and degeneration.

Neuron

January 2025

Departments of Psychiatry, Neuroscience, and Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX, USA; Peter O' Donnell Brain Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA. Electronic address:

DNA damage is a major risk factor for the decline of neuronal functions with age and in neurodegenerative diseases. While how DNA damage causes neurodegeneration is still being investigated, innovations over the past decade have provided significant insights into this issue. Breakthroughs in next-generation sequencing methods have begun to reveal the characteristics of neuronal DNA damage hotspots and the causes of DNA damage.

View Article and Find Full Text PDF

G-quadruplexes (G4s) are distinctive four-stranded nucleic acid structures formed by guanine-rich sequences, making them attractive targets for drug repurposing efforts. Modulating their stability and function holds promise for treating diseases like cancer. To identify potential drug candidates capable of interacting with these complex DNA formations, docking studies and molecular dynamics (MDs) simulations were conducted.

View Article and Find Full Text PDF

Want 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!