There are 15 different DNA polymerases encoded in mammalian genomes, which are specialized for replication, repair or the tolerance of DNA damage. New evidence is emerging for lesion-specific and tissue-specific functions of DNA polymerases. Many point mutations that occur in cancer cells arise from the error-generating activities of DNA polymerases. However, the ability of some of these enzymes to bypass DNA damage may actually defend against chromosome instability in cells, and at least one DNA polymerase, Pol ζ, is a suppressor of spontaneous tumorigenesis. Because DNA polymerases can help cancer cells tolerate DNA damage, some of these enzymes might be viable targets for therapeutic strategies.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3739438PMC
http://dx.doi.org/10.1038/nrc2998DOI Listing

Publication Analysis

Top Keywords

dna polymerases
20
dna damage
12
dna
9
cancer cells
8
polymerases cancer
4
cancer dna
4
polymerases
4
polymerases encoded
4
encoded mammalian
4
mammalian genomes
4

Similar Publications

DNA damage in cells induces the expression of inflammatory genes. However, the mechanism by which cells initiate an innate immune response in the presence of DNA lesions blocking transcription remains unknown. Here we find that genotoxic stresses lead to an acute activation of the transcription factor NF-κB through two distinct pathways, each triggered by different types of DNA lesions and coordinated by either ataxia-telangiectasia mutated (ATM) or IRAK1 kinases.

View Article and Find Full Text PDF
Article Synopsis
  • The TRAMP complex is crucial for RNA processing and features two key enzymatic activities that involve both polyadenylation and unwinding of RNA.
  • New research using hydrogen-deuterium exchange data reveals insights into how TRAMP assembles and shuffles RNA between its catalytic sites, which are not fully understood.
  • Findings indicate that peripheral RNA-recognition motifs affect TRAMP assembly and that different active-site subunits interact with tRNA in ways that influence RNA transfer between TRAMP components.
View Article and Find Full Text PDF

The DNA adducts formed by the alkenylbenzene natural products, safrole (SF) and methyleugenol (MEG) are primarily attributed to their reported carcinogenic properties. Herein, we report a concise strategy to access -Ac-SF/MEG-dA phosphoramidites, which were selectively incorporated into DNA oligonucleotides by solid-phase DNA synthesis. The replication studies using human polymerases hpolκ and hpolη showed that both polymerases replicate these adducts error-free, which indicates that these polymerases do not contribute to the adduct-induced mutagenicity.

View Article and Find Full Text PDF

Small molecules targeting the eubacterial β-sliding clamp discovered by combined and screening approaches.

J Enzyme Inhib Med Chem

December 2025

Laboratory of Biochemistry and Molecular Biology, Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parma, Italy.

Antibiotic resistance stands as the foremost post-pandemic threat to public health. The urgent need for new, effective antibacterial treatments is evident. Protein-protein interactions (PPIs), owing to their pivotal role in microbial physiology, emerge as novel and attractive targets.

View Article and Find Full Text PDF
Article Synopsis
  • The study investigates how somatic mitochondrial DNA mutations influence the development of leukemia, specifically through experiments with hematopoietic progenitor cells (HPCs) from genetically modified mice.
  • Researchers found that recipients of heterozygous mtDNA mutator HPCs had a higher spontaneous leukemia incidence, while homozygous mtDNA mutator HPCs had a lower incidence when combined with NMyc overexpression.
  • Both types of HPCs exhibited mitochondrial function impairments, but only heterozygous HPCs adapted to the metabolic demands of NMyc overexpression, as demonstrated by altered glucose utilization linked to metabolic changes in homozygous HPCs.
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!