All bacterial cells must duplicate their genomes prior to dividing into two identical daughter cells. Chromosome replication is triggered when a nucleoprotein complex, termed the orisome, assembles, unwinds the duplex DNA, and recruits the proteins required to establish new replication forks. Obviously, the initiation of chromosome replication is essential to bacterial reproduction, but this process is not inhibited by any of the currently-used antimicrobial agents. Given the urgent need for new antibiotics to combat drug-resistant bacteria, it is logical to evaluate whether or not unexploited bacterial processes, such as orisome assembly, should be more closely examined for sources of novel drug targets. This review will summarize current knowledge about the proteins required for bacterial chromosome initiation, as well as how orisomes assemble and are regulated. Based upon this information, we discuss current efforts and potential strategies and challenges for inhibiting this initiation pharmacologically.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6784150 | PMC |
| http://dx.doi.org/10.3390/antibiotics8030111 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Quantitative chromatin protein dynamics during replication origin firing in human cells.
Mol Cell Proteomics
January 2025
Center for Chromosome Stability, Institute for Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark.
Accurate genome duplication requires a tightly regulated DNA replication program, which relies on the fine regulation of origin firing. While the molecular steps involved in origin firing have been determined predominantly in budding yeast, the complexity of this process in human cells has yet to be fully elucidated. Here, we describe a straightforward proteomics approach to systematically analyse protein recruitment to the chromatin during induced origin firing in human cells.
View Article and Find Full Text PDFSister chromatid cohesion through the lens of biochemical experiments.
Curr Opin Cell Biol
January 2025
Department of Chromosome Science, National Institute of Genetics, Mishima, 411-8540, Japan; Department of Genetics, Graduate University for Advanced Studies (SOKENDAI), Mishima, 411-8540, Japan. Electronic address:
Faithful chromosome segregation in eukaryotes relies on physical cohesion between newly duplicated sister chromatids. Cohesin is a ring-shaped ATPase assembly that mediates sister chromatid cohesion through its ability to topologically entrap DNA. Cohesin, assisted by several regulatory proteins, binds to DNA prior to DNA replication and then holds two sister DNAs together when it encounters the replication machinery.
View Article and Find Full Text PDFPerturbation of peptidoglycan recycling by anti-folates and design of a dual-action inhibitor.
mBio
January 2025
Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
Unlabelled: Peptidoglycan (PG) is an important bacterial macromolecule that confers cell shape and structural integrity, and is a key antibiotic target. Its synthesis and turnover are carefully coordinated with other cellular processes and pathways. Despite established connections between the biosynthesis of PG and the outer membrane, or PG and DNA replication, links between PG and folate metabolism remain comparatively unexplored.
View Article and Find Full Text PDFTranscription near arrested DNA replication forks triggers ribosomal DNA copy number changes.
Nucleic Acids Res
January 2025
Laboratory of Genome Regeneration, Institute for Quantitative Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo113-0032, Japan.
Article Synopsis
- Sir2 is a histone deacetylase that helps maintain the stability of ribosomal RNA genes in budding yeast by preventing DNA breaks from leading to changes in rDNA copy number.
- It does this by suppressing transcription near issues that arise during DNA replication, which can otherwise provoke double-strand breaks (DSBs) and subsequent DNA repair processes.
- When Sir2 is absent, increased transcription can lead to DSBs, resulting in unstable rDNA copy numbers and the formation of extrachromosomal DNA, highlighting the importance of Sir2 in maintaining rDNA integrity.
RECQL4 requires PARP1 for recruitment to DNA damage, and PARG dePARylation facilitates its associated role in end joining.
Exp Mol Med
January 2025
Section on DNA Repair, Laboratory of Genetics and Genomics, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
RecQ helicases, highly conserved proteins with pivotal roles in DNA replication, DNA repair and homologous recombination, are crucial for maintaining genomic integrity. Mutations in RECQL4 have been associated with various human diseases, including Rothmund-Thomson syndrome. RECQL4 is involved in regulating major DNA repair pathways, such as homologous recombination and nonhomologous end joining (NHEJ).
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!