• 한국환경성돌연변이발암원학회지
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• 제18권2호
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• pp.71-76
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• 1998

환경독성물질에 의한 폭로는 세포내 DNA의 수복과정에 영향을 미쳐 돌연변이나 암을 유발할 수 있다. 독성물질에 의해 유도된 DNA의 비정상 수복효과를 판단하기 위하여.in vivo에서 MNNG 또는 Benzo(a)pyrene을 투여하고 in vitro에서 Bleomycin을 처리하여 나타나는 염색체이상효과를 관찰하였다. 실험결과, MNNG를 투여 후 Bleomycin을 처리하였을 때 염색체이상의 상승효과가 나타났다. 한편, Benzo(a)pyrene 투여 후 Bleomycin을 처리하였을 패는 높은 농도에서 염색체이상의 상승효과가 나타났다. 이같은 결과는 MNNG나 Benzo(a)pyrene 같은 유전독성물질들이 in vivo에서 세포내 비정상 DNA수복을 일으킬 수 있으며, 이러한 작용은 관련 유전독성물질의 염색체손상성에 무관하며 투여용량에 의존되는 것으로 판단된다.

• Journal of Genetic Medicine
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• 제13권1호
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• pp.1-13
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• 2016

Although some mutations are beneficial and are the driving force behind evolution, it is important to maintain DNA integrity and stability because it contains genetic information. However, in the oxygen-rich environment we live in, the DNA molecule is under constant threat from endogenous or exogenous insults. DNA damage could trigger the DNA damage response (DDR), which involves DNA repair, the regulation of cell cycle checkpoints, and the induction of programmed cell death or senescence. Dysregulation of these physiological responses to DNA damage causes developmental defects, neurological defects, premature aging, infertility, immune system defects, and tumors in humans. Some human syndromes are characterized by unique neurological phenotypes including microcephaly, mental retardation, ataxia, neurodegeneration, and neuropathy, suggesting a direct link between genomic instability resulting from defective DDR and neuropathology. In this review, rare human genetic disorders related to abnormal DDR and damage repair with neural defects will be discussed.

• Asian Pacific Journal of Cancer Prevention
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• 제16권12호
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• pp.4803-4812
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• 2015

Chronic alcohol and tobacco abuse plays a crucial role in the development of different liver associated disorders. Intake promotes the generation of reactive oxygen species within hepatic cells exposing their DNA to continuous oxidative stress which finally leads to DNA damage. However in response to such damage an entangled protective repair machinery comprising different repair proteins like ATM, ATR, H2AX, MRN complex becomes activated. Under abnormal conditions the excessive reactive oxygen species generation results in genetic predisposition of various genes (as ADH, ALDH, CYP2E1, GSTT1, GSTP1 and GSTM1) involved in xenobiotic metabolic pathways, associated with susceptibility to different liver related diseases such as fibrosis, cirrhosis and hepatocellular carcinoma. There is increasing evidence that the inflammatory process is inherently associated with many different cancer types, including hepatocellular carcinomas. The generated reactive oxygen species can also activate or repress epigenetic elements such as chromatin remodeling, non-coding RNAs (micro-RNAs), DNA (de) methylation and histone modification that affect gene expression, hence leading to various disorders. The present review provides comprehensive knowledge of different molecular mechanisms involved in gene polymorphism and their possible association with alcohol and tobacco consumption. The article also showcases the necessity of identifying novel diagnostic biomarkers for early cancer risk assessment among alcohol and tobacco users.

• Molecules and Cells
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• 제41권8호
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• pp.799-807
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• 2018

Emerging evidence has suggested that cellular crosstalk between RNF168 and poly(ADP-ribose) polymerase 1 (PARP1) contributes to the precise control of the DNA damage response (DDR). However, the direct and reciprocal functional link between them remains unclear. In this report, we identified that RNF168 ubiquitinates PARP1 via direct interaction and accelerates PARP1 degradation in the presence of poly (ADP-ribose) (PAR) chains, metabolites of activated PARP1. Through mass spectrometric analysis, we revealed that RNF168 ubiquitinated multiple lysine residues on PARP1 via K48-linked ubiquitin chain formation. Consistent with this, micro-irradiation-induced PARP1 accumulation at damaged chromatin was significantly increased by knockdown of endogenous RNF168. In addition, it was confirmed that abnormal changes of HR and HNEJ due to knockdown of RNF168 were restored by overexpression of WT RNF168 but not by reintroduction of mutants lacking E3 ligase activity or PAR binding ability. The comet assay also revealed that both PAR-binding and ubiquitin-conjugation activities are indispensable for the RNF168-mediated DNA repair process. Taken together, our results suggest that RNF168 acts as a counterpart of PARP1 in DDR and regulates the HR/NHEJ repair processes through the ubiquitination of PARP1.