Genotoxicity endpoints are useful tools to biomonitor the physicochemical and biological quality of aquatic ecosystems. A caging study on the freshwater bivalve Dreissena polymorpha was planned to run over four seasons in the Seine River basin in order to assess whether DNA damage measured in transplanted mussels to polluted area vary according to seasonal changes. Three sites were chosen along the Seine River, one upstream from Paris and two downstream, corresponding to a chemical gradient of water contamination. The DNA strand break (comet assay) and chromosomal damage (micronucleus test) were measured in caged mussels at each site and in winter, spring and summer, along with PAH water contamination, PAH bioaccumulation, the mussel condition index (CI), the gonado-somatic index (GSI) and the filtration rate (FR). The level of DNA strand break measured in winter was low and increased in spring, concomitantly with FR and GSI. Over the same period, micronucleus (MN) frequency and PAH bioaccumulation decreased significantly in caged mussels, with both parameters positively correlated to each other. DNA strand-break levels and MN frequencies showed inter-site variations corresponding to the chemical contamination gradient. These two genotoxicity endpoints usefully complement each other in field studies. These results show that the MN test and comet assay, when applied to gill cells of caged zebra mussels, are sensitive tools for freshwater genotoxicity monitoring.
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http://dx.doi.org/10.1016/j.ecoenv.2013.01.018 | DOI Listing |
Indian J Occup Environ Med
December 2024
Viral Research and Diagnostic Laboratory (VRDL), Government Medical College, Patiala, Punjab, India.
Pesticides induce oxidative DNA damage and genotoxic effects such as DNA single-strand breaks (SSBs), double-strand breaks (DSBs), DNA adducts, chromosomal aberrations, and enhanced sister chromatid exchanges. Such DNA damage can be repaired by DNA repair mechanisms. In humans, single nucleotide polymorphisms (SNPs) are present in DNA repair genes involved in base excision repair (BER) (, and nucleotide excision repair (NER) (, , , and ), and double-strand break repair (DSBR) ( and ).
View Article and Find Full Text PDFMech Ageing Dev
January 2025
Department of Biological Science, College of Natural Science, Chosun University, 309 Pilmun-daero, Dong-gu, Gwangju 61452, Republic of Korea; BK21 FOUR Education Research Group for Age-Associated Disorder Control Technology, Department of Integrative Biological Science, Chosun University, Gwangju 61452, Republic of Korea; The Basic Science Institute of Chosun University, Chosun University, Gwangju 61452, Republic of Korea. Electronic address:
The protective effects of mangiferin (MAG) against etoposide- and high glucose (HG)-induced DNA damage and aging were investigated in human bone marrow-mesenchymal stem cells (hBM-MSCs). Etoposide, a topoisomerase II inhibitor, was used to induce double-strand breaks (DSBs) in hBM-MSCs, resulting in increased genotoxicity, elevated levels of the DNA damage sensor ATM and CDKN1A, and decreased levels of the aging markers H3 and H4. MAG activated AMPK and SIRT1, thus protecting against DSB-induced damage.
View Article and Find Full Text PDFIntegration of DNA replication with DNA repair, cell cycle progression, and other biological processes is crucial for preserving genome stability and fundamentally important for all life. Ataxia-telangiectasia mutated and RAD3-related (ATR) and its partner ATR-interacting protein (ATRIP) function as a critical proximal sensor and transducer of the DNA Damage Response (DDR). Several ATR substrates, including p53 and CHK1, are crucial for coordination of cell cycle phase transitions, transcription, and DNA repair when cells sustain DNA damage.
View Article and Find Full Text PDFA previous study found that a domesticated bacterial group II intron-like reverse transcriptase (G2L4 RT) functions in double-strand break repair (DSBR) via microhomology-mediated end joining (MMEJ) and that a mobile group II intron-encoded RT has a basal DSBR activity that uses conserved structural features of non-LTR-retroelement RTs. Here, we determined G2L4 RT apoenzyme and snap-back DNA synthesis structures revealing novel structural adaptations that optimized its cellular function in DSBR. These included a unique RT3a structure that stabilizes the apoenzyme in an inactive conformation until encountering an appropriate substrate; a longer N-terminal extension/RT0-loop with conserved residues that together with a modified active site favors strand annealing; and a conserved dimer interface that localizes G2L4 RT homodimers to DSBR sites with both monomers positioned for MMEJ.
View Article and Find Full Text PDFNat Commun
January 2025
Robson DNA Science Centre, Charbonneau Cancer Institute, Department of Biochemistry & Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
To tolerate oxidative stress, cells enable DNA repair responses often sensitive to poly(ADP-ribose) (PAR) polymerase 1 and 2 (PARP1/2) inhibition-an intervention effective against cancers lacking BRCA1/2. Here, we demonstrate that mutating the CHD6 chromatin remodeler sensitizes cells to PARP1/2 inhibitors in a manner distinct from BRCA1, and that CHD6 recruitment to DNA damage requires cooperation between PAR- and DNA-binding domains essential for nucleosome sliding activity. CHD6 displays direct PAR-binding, interacts with PARP-1 and other PAR-associated proteins, and combined DNA- and PAR-binding loss eliminates CHD6 relocalization to DNA damage.
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