• Journal of Photoscience
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• 제9권2호
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• pp.186-189
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• 2002

Many of the adverse effects of solar UV exposure appear to be directly attributable to damage to epidermal DNA. In particular, cyclobutane pyrimidine dimers (CPD) may initiate mutagenic changes as well as induce signal transduction responses that lead to a loss of skin immune surveillance and micro-destruction of skin structure. Our approach is to reverse the DNA damage using prokaryotic DNA repair enzymes delivered into skin using specially engineered liposomes. T4 endonuclease V encapsulated in liposomes (T4N5 liposome lotion) enhanced DNA repair by shifting repair of CPD from the nucleotide excision to the base excision repair pathway. Following topical application to humans, increased repair limited UV-induction of cytokines, many of which are immunosuppressive. In a recent clinical study, topical treatment of UV-irradiated human skin with T4N5 liposome lotion reduced the suppression of the nickel sulfate contact hypersensitivity response. Similarly, the photoreactivating enzyme enhances repair by directly reversing CPDs after absorbing activating light. Here also treatment of UV-irradiated human skin with photoreactivating enzyme in liposomes and photoreactivating light restored the response to the contact allergen nickel sulfate. These findings confirm in humans the observation in mice that UV induced suppression of contact hypersensitivity is caused in part by CPDs. We have tested the ability of T4N5 liposome lotion to prevent UV-induced skin cancer in patients with xeroderma pigmentosum (XP), who have an elevated incidence of skin cancer resulting from a genetic defect in DNA repair. Daily use of the lotion for one year in a group of 20 XP patients reduced the average number of actinic keratoses by 68% and basal cell cancers by 30% compared to 9 patients in the placebo control group. Delivery of DNA repair enzymes to skin is a promising new approach to photoprotection.

• 한국동물학회지
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• 제20권1호
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• pp.41-48
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• 1977

Bleomycin에 의해 유발된 DNA 회복합성은 저농도 처리군에서는 농도의 증가에 따라 증가하며 $5\\mu$g/ml 군에서 조사한 전세포의 15%가 회복합성을 하여 최고율을 보인다. 고농도 처리군에서 DNA 회복합성율이 감소하며 처리 시간을 연장해도 그율은 변화가 없다. BUdR이나 IUdR을 전처리한군에서는 DNA회복합성을 증가시키는 것으로 판명됐으며 또한 고동도 처리군에서는 정상적인 DNA 합성을 억제한다. 시간 변화에 따른 실험에서는 처리한 bleomycin을 제거한후 24시간까지 DNA 회복합성이 계속됐다. 이들 결과는 bleomycin이 excision repair를 유발하는 효과적인 화학물질이 아니며, bleomycin에 의해 유발되는 DNA의 손상은 DNA 나선 절단뿐만 아니라 다른 형태의 DNA 손상도 유발함을 추측할수 있다.

• 한국환경성돌연변이발암원학회지
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• 제8권1호
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• pp.1-12
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• 1988

본 연구는 Ethyl methanesulfonato(EMS) 혹은 Bleomycin(BLM)에 의해 유발된 DNA상해의 회복에 미치는 DNA 종합효소 $\alpha$ 저해제인 Aphidicolin(APC)과 DNA 종합효소 $\beta$의 저해제인 2`, 3`-dideoxythymididine 5`-triphosphate(ddTTP)의 영향을 조사하기 위하여 Chinese hamster ovary(CHO)-Kl 세포를 재료로 비주기성 DNA 합성법과 알칼리유출법 및 스칼리 자당구배침강법으로 수행하여 얻은 결과는 다음과 같다. APC와 ddTTP는 EMS에 의해 유발된 DNA 상해의 회복을 저해하여 APC 혹은 ddTTP를 처리하지 않고 배양한 실험군 보다 비주기성 DNA 합성율과 DNA 단사 절단율이 증가되었다. 한편 BLM에 의해 유발된 DNA 상해의 회복에서는 ddTTP를 처리했을 경우에만 저해되었다. 즉 BLM 처리 후 ddTTP를 후처리한 실험군의 비주기성 DNA 합성율과 DNA단사 절단율은 ddTTP를 처리하지 않은 군보다 증가되었고, BLM 처리 후 APC를 후처리할 경우에 비주기성 DNA 합성율과 DNA 단사 절단율은 APC를 처리하지 않은 군과 유사하였다. 이상의 결과들에서 EMS에 의해 유발된 DNA 상해의 회복에는 DNA 중합효소 $\alpha$, $\beta$양자가 관여하나 BLM에 의해 유발된 DNA 상해의 회복에는 중합효소 $\beta$가 관여하는 것으로 추측된다.

• Archives of Pharmacal Research
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• 제18권4호
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• pp.243-248
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• 1995

Seventeen transformation-deficient mutants of streptococcus pneumoniae, which are defective in competence induction (com), DNA uptake(ent) of recombination(rec), were investigated to determine sensitivity to ethylmethane sulfonate(EMS), methylmethane sulfonate(MMS), UV and mitomycin C. In ethylmethane sulfonate assay, the viability of most $com^-, \; rec^-\; and ent^-$ mutants was decreased about 2-10 times and the viability of ent-9 and ent-13 mutant was decreased about 33 and 25 times, respectively. On the other hand only half of the transformation-deficient mutants tested was sensitive to methylmethane sulfonate about 2 times and ent-12 mutant was sensitive to 2.0% MMS about 8 times. After UV and mitomycin C treatment, most of the mutants are not sensitive to UV and mitomycin C, although the viability of some transformation-deficient mutants was decreased slightly. Especially none of the com mutants were sensitive to DNA damage suggesting that competence is not involved in DNA repair. Also DNA uptake and recombination gane might be related to DNA repair function.

• Journal of Photoscience
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• 제9권2호
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• pp.479-481
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• 2002

UV-induced DNA damage causes cell killing and mutations leading to carcinogenesis. In normal human cells, UV damage such as cyclobutane pyrimidine dimers (CPDs) and primidine-prymidone (6-4) photoproducts are mainly repaired by nucleotide excision repair mechanism. The molecular processes have been well characterized recently. To know the influence of mitochondrial genome on the nucleotide excision repair mechanism against CPDs, we comparatively examined the production of CPDs by UVC irradiation and their repair kinetics in human cells completely lacking mitochondrial DNA (mtDNA) and the parental HeLa S cells. Whole DNA extracted from the cells exposed to UVC was treated with T4-endonuclease V to break the phosphodiester bond adjacent to CPDs. The DNA was electrophoresed in a denaturing agarose gel, which was visualized by ethidium bromide staining. The relative amount of CPDs was determined by image analysis using NIH Image software. MtDNA- less (rho-O) cells were apparently more sensitive to UVC than HeLa S cells, while the level of induction of CPDs in rho-O and HeLa cells was comparable. The repair of CPDs was less efficient in rho-O cells compared with HeLa cells. The residual amount of CPDs after 24-h repair was larger in rho-O cells than in HeLa cells where more than 90 % of CPDs were repaired by then. The non-repaired CPDs would lead to apoptosis in rho-O cells. These results suggest that mitochondrial genome may contribute to some ATP-dependent steps in nucletide excision repair by supplying sufficient ATP which is generated through a respiratory chain in mitochondria.

• 한국환경성돌연변이발암원학회지
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• 제9권1호
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• pp.13-22
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• 1989

The effect of novobiocin (NOV), and inhibitor of topoisomerase II, on ethyl methanesulfonate (EMS)-or bleomycin (BLM)-induced DNA repair synthesis was examined during the cell cycle of Chinese hamster ovary (CHO)-K1 cells. Three assays were employed in this study: cell survival, alkaline elution and unscheduled DNA synthesis. EMS was effective at killing CHO cells in G1 phase, wheras BLM preferentially killed cells in G2 and S phases. EMS induced the much more amount of DNA damage in G1 phase, while BLM induced in G2 phase than the other phases. The both of pre- and post-treatment with BOV inhibitied EMS- or BLM-induced DNA repair synthesis in G1 and G2 phases, and pretreatment with NOV inhibited more effectively than the post-treated group. These results suggested that CHO cells exhibited a differential sensitivity to cell lethality and DNA damage in relation to cell cycle according to used chemical agents, and that DNA topoisomerase II participated in an initial stage of DNA repair.

• 한국환경성돌연변이발암원학회지
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• 제11권2호
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• pp.107-117
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• 1991

The effect of 3-aminobenzamide (3AB), an inhibitor of poly (ADP-ribose) polymerase, on ethyl methanesulfonate (EMS)-or bleomycin (BLM)-induced DNA repair synthesis and chromosome aberrations was examined during the cell cycle of Chinese hamster ovary (CHO)-K$_1$ cells. The synchronized cells were obtained by using thymidine double block method and mitotic selection method. Three assays were employed in this study: unscheduled DNA synthesis, alkaline elution and chromosome aberrations. 3AB alone did not induce DNA repair and chromosome aberrations in all phases. The post-treatment with 3AB inhibited DNA repair synthesis induced by EMS or BLM in G$_2$ phase, whereas 3AB did not affect chromosome aberrations induced by EMS or BLM in all phases. These results suggest that 3AB aggravates the cell cycle disturbance which occur after DNA damage, and leads to an accumulation of cells at G$_2$ phase, and inhibits DNA repair synthesis, while the effect 3AB on chromosome aberrations may need reevaluated.

• Molecules and Cells
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• 제19권2호
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• pp.167-179
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• 2005

The cells of metazoans respond to DNA damage by either arresting their cell cycle in order to repair the DNA, or by undergoing apoptosis. This response is highly conserved across species, and many of the genes involved in this DNA damage response have been shown to be inactivated in human cancers. This suggests the importance of DNA damage response with regard to the prevention of cancer. The DNA damage checkpoint responses vary greatly depending on the developmental context, cell type, gene expression profile, and the degree and nature of the DNA lesions. More valuable information can be obtained from studies utilizing whole organisms in which the molecular basis of development has been well established, such as Drosophila. Since the discovery of the Drosophila p53 orthologue, various aspects of DNA damage responses have been studied in Drosophila. In this review, I will summarize the current knowledge on the DNA damage checkpoint response in Drosophila. With the ease of genetic, cellular, and cytological approaches, Drosophila will become an increasingly valuable model organism for the study of mechanisms inherent to cancer formation associated with defects in the DNA damage pathway.

• 한국식품영양학회지
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• 제33권3호
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• pp.309-316
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• 2020

In this study, we investigated the protective effects of Ulva lactuca methanol extracts against ultraviolet B (UVB)-induced DNA damage in HaCaT cells. First, the contents of general and antioxidative nutrient contents of Ulva lactuca were measured. The moisture, carbohydrate, crude protein, crude fat and ash were 14.01%, 44.80%, 23.19%, 3.10% and 14.90%, respectively. Magnesium that acts as DNA repair enzyme cofactor was the most abundant mineral followed by Ca, P and Fe. The total phenolic and anthocyanoside contents of Ulva lactuca were 2.69 mg/g and 0.13 mg/g, respectively. Cells treated with Ulva lactuca methanol extracts for 24 hours post UVB exposure increased cell viability in a concentration-dependent manner compared to the non-treated control. Also, Ulva lactuca methanol extracts decreased the levels of UVB-induced DNA damage such as cyclobutane pyrimidine dimer and DNA damage response (DDR) proteins such as p-p53 and p21. These results suggest that Ulva lactuca methanol extracts comprising physiological active substances such as Mg, polyphenols and anthocyanosides promote DNA repair by regulating genes related with DDR.

• Bioinformatics and Biosystems
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• 제2권1호
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• pp.12-16
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• 2007

DNA repair means a collection of processes that a cell identifies and corrects damage to genome sequence. The DNA repair processes are important because a genome would not be able to maintain its essential cellular functions without the processes. In this research, we make some gene regulatory networks of DNA repair in S. cerevisiae to know how each gene interacts with others. Two approaches are adapted to make the networks; Bayesian Network and ARACNE. After construction of gene regulatory networks based on the two approaches, the two networks are compared to each other to predict which genes have important roles in the DNA repair processes by finding conserved interactions and looking for hubs. In addition, each interaction between genes in the networks is validated with interaction information in S. cerevisiae genome database to support the meaning of predicted interactions in the networks.