Background: Previous studies have suggested that variations in DNA repair genes of W-Beijing strains may have led to transient mutator phenotypes which in turn may have contributed to host adaptation of this strain family. Single nucleotide polymorphism (SNP) in the DNA repair gene mutT1 was identified in MDR-prone strains from the Central African Republic. A Mycobacteriumtuberculosis H37Rv mutant inactivated in two DNA repair genes, namely ada/alkA and ogt, was shown to display a hypermutator phenotype. We then looked for polymorphisms in these genes in Central African Republic strains (CAR).
Results: In this study, 55 MDR and 194 non-MDR strains were analyzed. Variations in DNA repair genes ada/alkA and ogt were identified. Among them, by comparison to M. tuberculosis published sequences, we found a non-sense variation in ada/alkA gene which was also observed in M. bovis AF2122 strain. SNPs that are present in the adjacent regions to the amber variation are different in M. bovis and in M. tuberculosis strain.
Conclusion: An Amber codon was found in the ada/alkA locus of clustered M. tuberculosis isolates and in M. bovis strain AF2122. This is likely due to convergent evolution because SNP differences between strains are incompatible with horizontal transfer of an entire gene. This suggests that such a variation may confer a selective advantage and be implicated in hypermutator phenotype expression, which in turn contributes to adaptation to environmental changes.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1891112 | PMC |
http://dx.doi.org/10.1186/1471-2180-7-39 | DOI Listing |
EMBO Rep
January 2025
Department of Biochemistry, University of Toronto, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada.
Homologous recombination is a largely error-free DNA repair mechanism conserved across all domains of life and is essential for the maintenance of genome integrity. Not only are the mutations in homologous recombination repair genes probable cancer drivers, some also cause genetic disorders. In particular, mutations in the Bloom (BLM) helicase cause Bloom Syndrome, a rare autosomal recessive disorder characterized by increased sister chromatid exchanges and predisposition to a variety of cancers.
View Article and Find Full Text PDFExp 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 PDFNat Commun
January 2025
Mechanisms, Biomarkers and Models Section - Genome Stability Group, Department of Environment and Health, Istituto Superiore di Sanità, Viale Regina Elena, 299 - 00161, Rome, Italy.
The WRN protein is vital for managing perturbed replication forks. Replication Protein A strongly enhances WRN helicase activity in specific in vitro assays. However, the in vivo significance of RPA binding to WRN has largely remained unexplored.
View Article and Find Full Text PDFCell Death Discov
January 2025
Institute of Biopharmaceutical Sciences, College of Pharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan.
TP53 mutations are recognized to correlate with a worse prognosis in individuals with non-small cell lung cancer (NSCLC). There exists an immediate necessity to pinpoint selective treatment for patients carrying TP53 mutations. Potential drugs were identified by comparing drug sensitivity differences, represented by the half-maximal inhibitory concentration (IC50), between TP53 mutant and wild-type NSCLC cell lines using database analysis.
View Article and Find Full Text PDFMelanoma Manag
December 2024
Supportive Care Dep, Institut Curie, Paris, France.
Metastatic uveal melanoma (UM) patients often initially present with limited symptoms despite a poor prognosis, complicating communication with patients and caregivers. Early Together (NCT04728113) is a randomized Phase III trial that integrates early palliative care through systematic joint visits involving the palliative care team and the medical oncologist, compared with standard oncological care, in 162 metastatic UM patients beginning systemic treatment. This collaboration aims to enhance patient functioning, improve quality of life and facilitate coping mechanisms.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!