To investigate UV light response mechanisms in higher plants, we isolated a UV light-sensitive mutant, rev3-1, in Arabidopsis. The root growth of rev3-1 was inhibited after UV-B irradiation under both light and dark conditions. We found that chromosome 1 of rev3-1 was broken at a minimum of three points, causing chromosome inversion and translocation. A gene disrupted by this rearrangement encoded the catalytic subunit of DNA polymerase zeta (AtREV3), which is thought to be involved in translesion synthesis. The rev3-1 seedlings also were sensitive to gamma-rays and mitomycin C, which are known to inhibit DNA replication. Incorporation of bromodeoxyuridine after UV-B irradiation was less in rev3-1 than in the wild type. These results indicate that UV light-damaged DNA interrupted DNA replication in the rev3-1 mutant, leading to the inhibition of cell division and root elongation.
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http://dx.doi.org/10.1105/tpc.012369 | DOI Listing |
J Org Chem
January 2025
Department of Chemistry, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India.
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 PDFAppl Environ Microbiol
December 2024
Ocean College, Zhejiang University, Zhoushan, China.
This study explored the genomic alterations in , a key yeast in industrial biotechnology, under both spontaneous and mutagen-induced conditions. Our findings reveal that spontaneous mutations occur at a rate of approximately 4 × 10 events per base pair per cell division, primarily manifesting as single-nucleotide variations (SNVs) and small insertions and deletions (InDels). Notably, C-to-T/G-to-A transitions and C-to-A/G-to-T transversions dominate the spontaneous SNVs, while 1 bp deletions, likely resulting from template slippage, are the most frequent InDels.
View Article and Find Full Text PDFGenetics
December 2024
Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425, USA.
Acetaldehyde is the primary metabolite of alcohol and is present in many environmental sources including tobacco smoke. Acetaldehyde is genotoxic, whereby it can form DNA adducts and lead to mutagenesis. Individuals with defects in acetaldehyde clearance pathways have increased susceptibility to alcohol-associated cancers.
View Article and Find Full Text PDFNucleic Acids Res
December 2024
Department of Biological Sciences, Ulsan National Institute of Science and Technology (UNIST), UNIST-gil 50, Ulsan 44919, Republic of Korea.
In a comprehensive study to decipher the multi-layered response to the chemotherapeutic agent temozolomide (TMZ), we analyzed 427 genomes and determined mutational patterns in a collection of ∼40 isogenic DNA repair-deficient human TK6 lymphoblast cell lines. We first demonstrate that the spontaneous mutational background is very similar to the aging-associated mutational signature SBS40 and mainly caused by polymerase zeta-mediated translesion synthesis (TLS). MSH2-/- mismatch repair (MMR) knockout in conjunction with additional repair deficiencies uncovers cryptic mutational patterns.
View Article and Find Full Text PDFPer Med
December 2024
Hanoi Medical University, Hanoi city, Vietnam.
Xeroderma pigmentosum (XP) disorder is recognized as a genetic condition inherited by autosomal recessive fashion. XP results from a defective DNA repair mechanism that significantly increases skin cancer risk. Fifteen Vietnamese patients were investigated with typical clinical manifestations of XP.
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