• BMB Reports
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• 제41권3호
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• pp.230-235
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• 2008

LRP15 is a novel gene cloned from lymphocytic cells, and its function is still unknown. Bioinformatic data showed that LRP15 might be regulated by DNA methylation and had an important role in DNA repair. In this study, we investigate whether the expression of LRP15 is regulated by DNA methylation, and whether overexpression of LRP15 increases efficiency of DNA repair of UV-induced DNA damage in HeLa cells. The results showed (1) the promoter of LRP15 was hypermethylated in HeLa cells, resulting a silence of its expression. Gene expression was restored by a demethylating agent, 5-aza-2'-deoxycytidine, but not by a histone deacetylase inhibitor, trichostatin A; (2) overexpression of LRP15 inhibited HeLa cell proliferation, and the numbers of cells in the G2/M phase of the cell cycle in cells transfected with LRP15 increased about 10% compared with controls; (3) cyclin B1 level was much lower in cells overexpressing LRP15 than in control cells; and (4) after exposure to UV radiation, the LRP15-positive cells showed shorter comet tails compared with the LRP15-negative cells. From these results we conclude that the expression of LRP15 is controlled by methylation in its promoter in HeLa cells, and LRP15 confers resistance to UV damage and accelerates the DNA repair rate.

• 한국동물학회지
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• 제26권3호
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• pp.171-179
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• 1983

MMS와 자외선에 의한 DNA의 절제회복과 단사절단에 미치는 poly(ADP-ribose) polymerase의 저해제인 3-aminobenzamide의 영향을 CHO 세포를 재로로 조사하여 다음과 같은 결과를 얻었다. 1. MMS에 의한 비주기성 DNA 합성률과 DNA 단사 절단률은 이 저해제에 의해 모두 증가하였다. 이는 poly (ADP-ribose) polymeraserk MMS에 의해 유발된 염기 절제회복의 incision step를 억제하는 결과라 생각된다. 2. 자외선에 의한 비주기성 DNA 합성률과 DNA단사 절단률은 이 저해제에 의해 모두 감소하였다. 이는 poly(ADP-ribose) polymerase가 자외선에 의해 유발된 nucleotide 절제회복의 incision step을 돕는 작용을 하는 결과로 생각된다. 3. MMS와 자외선을 복합처리한 실험군에서는, DNA 단사 절단률은 이 저해제에 의해 영향을 받지 않았으며, 비주기성 DNA 합성률은 자외선 단독 처리군의 수준으로 증가되었다. 이는, 이 저해제가 MMS와 자외선으로 유발된 절제회복의 incision step에는 독립적으로 작용하며, 그 이후의 단계에서, MMS에 의해 부분적으로 불활성화 되었던 pyrimidine dimers의 절제를 완전하게 해주는 것으로 해석된다.

• 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.

• 한국정보통신학회논문지
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• 제15권11호
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• pp.2500-2504
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• 2011

살아있는 생명체는 세포로 구성되며 성장 분열을 통해 스스로 복제할 수 있는 능력을 지녔다. DNA상의 변이, 즉 돌연변이는 자손의 생존과 번식에 불리하게 작용할 수 있고 이점을 줄 수 있는 양면성을 지녔다. 본 연구에서는 DNA 이중나선은 복제 주형으로 사용되기 위해서는 먼저 이중나선이 열리고 단일 가닥으로 분리되어야 한다. 이중 나선구조결합에서의 결합의 오류부분의 위치를 찾아내고 복구하는 방법을 제시한다.

• Journal of Photoscience
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• 제9권2호
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• pp.182-185
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• 2002

There are 3 UV DNA repair endonuclease activities in mammalian cells that cleave UV -irradiated DNA. Interestingly, mammalian UV endonuclease III with MW of 26.7kD has a lyase activity on AP sites. It also cleaves the phosphodiester bond within a cyclobutane pyrimidine dimer. Genomic analysis of human repair endonuclease III gene revealed that this gene has 100% sequence identity with ribosomal protein S3 (rpS3). Therefore, rpS3 seems to function both in translation and in DNA repair. This gene of about 6.1 kb contains 6 introns and 7 exons, and the first and fifth introns of human rpS3 gene contain functional U15 small nucleolar (sno) RNAs which appear to be involved in ribosome assembly. It is to be noted that the column profile of the endonuclease activity of rpS3 appears to be altered in Xeroderma Pigmentosum (XP) group D cells compared to normal cells indicating that this protein is involved in XP disease as well. XP is a human disease characterized by high sensitivity of skin by UV- or sun-light irradiation and by high frequency of developing skin cancers. We also report here that rpS3 protein is involved in other cellular functions.

• Asian Pacific Journal of Cancer Prevention
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• 제16권15호
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• pp.6385-6390
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• 2015

Background: Genetic polymorphisms in DNA repair genes may influence individual variation in DNA repair capacity, which may be associated with risk of developing cancer. For colorectal cancer the importance of mutations in mismatch repair genes has been extensively documented. Materials and Methods: In this study we focused on the Arg194Trp polymorphism of the DNA repair gene XRCC1, involved in base excision repair (BER) and its role in colorectal cancer in Kashmiri population. A case-control study was conducted including 100 cases of colorectal cancer, and 100 hospital-based age- and sex-matched healthy controls to examine the role of XRCC1 genetic polymorphisms in the context of colorectal cancer risk for the Kashmiri population. Results: Genotype analysis of XRCC1 Arg194Trp was conducted with a restriction fragment length polymorphism (RFLP) method. The overall association between the XRCC1 polymorphism and the CRC cases was found to be significant (p < 0.05) with both the heterozygous genotype (Arg/Trp) as well as homozygous variant genotype (Trp/Trp) being moderately associated with the elevated risk for CRC [OR=2.01 (95% CI=1.03-3.94) and OR=5.2(95% CI=1.42-19.5)] respectively. Conclusions: Our results suggest an increased risk for CRC in individuals with XRCC1 Arg194Trp polymorphism suggesting BER repair pathway modulates the risk of developing colorectal cancer in the Kashmiri population.

• BMB Reports
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• 제51권9호
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• pp.437-443
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• 2018

Non-homologous end joining (NHEJ), and to a lesser extent, the error-free pathway known as homology-directed repair (HDR) are cellular mechanisms for recovery from double-strand DNA breaks (DSB) induced by RNA-guided programmable nuclease CRISPR/Cas. Since NHEJ is equivalent to using a duck tape to stick two pieces of metals together, the outcome of this repair mechanism is prone to error. Any out-of-frame mutations or premature stop codons resulting from NHEJ repair mechanism are extremely handy for loss-of-function studies. Substitution of a mutation on the genome with the correct exogenous repair DNA requires coordination via an error-free HDR, for targeted transgenesis. However, several practical limitations exist in harnessing the potential of HDR to replace a faulty mutation for therapeutic purposes in all cell types and more so in somatic cells. In germ cells after the DSB, copying occurs from the homologous chromosome, which increases the chances of incorporation of exogenous DNA with some degree of homology into the genome compared with somatic cells where copying from the identical sister chromatid is always preferred. This review summarizes several strategies that have been implemented to increase the frequency of HDR with a focus on somatic cells. It also highlights the limitations of this technology in gene therapy and suggests specific solutions to circumvent those barriers.

• Journal of Microbiology
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• 제39권2호
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• pp.102-108
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• 2001

DNA damage response has a central role in the maintenance of genomic integrity while mutations in related genes may result in a range of disorders including neoplasic formations. The uvsZl characterized in this report is a navel uvs mutation in Aspergillus nidulans, resulting in a nucleotide excision repair (NER) phenotype: UV-sensitivity before DNA synthesis (quiescent cells), high UV-induced mutation frequency and probable absence of involvement with mitotic and meiotic recombinations. The mutation is recessive and nan-allelic to the previously characterized uvsA101 mutation, also located on the paba-y interval on chromosome I. uvsZl skewed wild-type sensitivity to MMS, which suggests non-involvement of this mutation with BER. Epitasis tests showed that the uvsZ gene product is probably involved in the same repair pathways as UVSB or UVSH proteins. Although mutations in these proteins result in an NER phenotype, UVSB is related with cell cycle control and UVSH is associated with the post-replicational repair pathway. The epistatic interaction among uvsZl and uvsB413 and uvsH77 mutations indicates that different repair systems may be related with the common steps of DNA damage response in Aspergillus nidulans.

• 한국정보통신학회:학술대회논문집
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• 한국정보통신학회 2012년도 추계학술대회
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• pp.293-297
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• 2012

세포에서 질서를 유지하기 위해서는 유전정보에 대한 지속적인 감시와 회복체계를 필요로 한다. DNA는 염기쌍의 결합으로 이루어지는데, 틀린 염기쌍이 정상적인 염기쌍보다 훨씬 낮은 빈도로 형성되지만, 이것이 수정되지 않고 DNA내에 축적될 경우 세포가 죽기도 한다. 본 연구에서는 DNA 복제 시 발생하는 실수, 손상된 부분을 회복하는 DNA 복구 기능을 모사하여 공학적인 개념을 도입한다. 기존에 발표 되었던 부분을 보완하여 여러 군데에서 발생한 오류 위치를 찾아내고 복구시키는 효율적인 알고리즘을 제시한다.

• 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.