The base excision repair carried out by bacterial MutY DNA glycosylase and eukaryotic MutY homolog (MYH) is responsible for removing adenines misincorporated into DNA opposite G and 7,8-dihydro-8-oxo-guanines (8-oxoG); thereby preventing G:C to T:A mutations. Escherichia coli MutY (EcMutY) can also remove adenines from A/C and A/5-hydroxyuracil and can remove guanines from G/8-oxoG mismatches at reduced rates. Thus, MutY has a minor role in reducing the mutagenic effects on G:C to A:T transitions and G:C to C:G transversions. The eukaryotic MYH can excise adenines misincorporated opposite GO, G, or C; remove 2-hydroxyadenines mispaired with A,G, and GO; excise G from G/GO mismatch weakly, thereby preventing G:C to T:A transversions. The in vitro and in vivo activities of MYH can be modulated by several proteins including apurinic/apyrimidinic endonuclease (APE1), proliferating cell nuclear antigen (PCNA), and mismatch recognition enzymes MSH2/MSH6. Recently, MYH has been shown to associate with the checkpoint proteins, Rad9, Rad1, and Hus1 (referred as the 9-1-1 complex). Thus, MYH-mediated base excision repair is coordinated with mismatch repair, DNA replication, cell-cycle progression, and DNA-damage checkpoints. Biallelic germ-line mutations in the human MYH gene are associated with recessive inheritance of multiple colorectal adenomas and carcinoma. MYH mutations can cause G:C to T:A mutations of the adenomatous polyposis coli (APC), K-ras, and other genes that control cellular proliferation in the colon.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.2741/2033 | DOI Listing |
The [4Fe-4S] cluster is an important cofactor of the base excision repair (BER) adenine DNA glycosylase MutY to prevent mutations associated with 8-oxoguanine (OG). Several MutYs lacking the [4Fe-4S] cofactor have been identified. Phylogenetic analysis shows that clusterless MutYs are distributed in two clades suggesting cofactor loss in two independent evolutionary events.
View Article and Find Full Text PDFDefects in DNA single-strand break repair are associated with neurodevelopmental and neurodegenerative disorders. One such disorder is that resulting from mutations in , a scaffold protein that plays a central role in DNA single-strand base repair. XRCC1 is recruited at sites of single-strand breaks by PARP1, a protein that detects and is activated by such breaks and is negatively regulated by XRCC1 to prevent excessive PARP binding and activity.
View Article and Find Full Text PDFJAAD Case Rep
January 2025
Department of Dermatology, Assistant Director-The Humanitarian Clinic: Skin, Hair and Laser Centre, Mumbai, Maharashtra, India.
J Ayurveda Integr Med
January 2025
Centre for Ayurvedic Biology, Department of Ageing Research, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, 576104, Karnataka, India. Electronic address:
Background: Brain ageing is accompanied by the diminution of neuronal plasticity, which is correlated with the inability to respond to loss of memory, various stress-induced stimuli, and increased risk of neurodegenerative disorders. In the recent past, plant based herbal medicines are of interest over synthetic drugs for therapeutic purposes due to lower side effects. The Indian traditional medicine Ayurveda describes several herbal remedies, such as rasayana (elixirs for rejuvenation), to treat many age-related diseases.
View Article and Find Full Text PDFNucleic Acids Res
January 2025
Department of Physics, 845 W Taylor St, University of Illinois Chicago, Chicago, IL 60607, USA.
Altered DNA dynamics at lesion sites are implicated in how DNA repair proteins sense damage within genomic DNA. Using laser temperature-jump (T-jump) spectroscopy combined with cytosine-analog Förster Resonance Energy Transfer (FRET) probes that sense local DNA conformations, we measured the intrinsic dynamics of DNA containing 3 base-pair mismatches recognized in vitro by Rad4 (yeast ortholog of XPC). Rad4/XPC recognizes diverse lesions from environmental mutagens and initiates nucleotide excision repair.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!