• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제34권5호
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• pp.509-517
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• 2008

DNA 손상 치유 유전자 연구를 기초로 한 임상적 접근이 새로운 치료방법으로 떠오르고 있다. 많은 연구들이 중요한 DNA 수복유전자의 다형성을 찾아내어 각각의 단백질의 활동성에 대한 영향을 알아내고 특정한 치료법을 찾아내고 임상적 적용을 시도하고 결과를 평가하였다. 그 결과 암 치료에서 정상 세포와 암세포에서 DNA 수복 유전자의 발현 분석은 화학요법이나 방사선 치료에서 개인맞춤형 치료법을 가능하게 하고 있다. 예를 들어, NER이 결핍된 종양은 cisplatin 치료에 민감성을 나타내고, MMR 결핍세포는 알킬화 화학요법 약제에 높은 내성을 나타낸다. 선천성 비폴립성 결장암과 같은 MMR 결손종양 또한 알킬화 화학요법 약제에 의한 치료에 내성을 가진다. 신경교종(glioma)에서 MGMT 유전자 프로모터가 흔히 메틸화되는데 이것은 유전자 발현이 억제되고 알킬화 화학요법제에 대한 반응성을 증가시킨다. 향후 구강악안면외과 영역에서도 구강암의 발생의 위험성을 증가시킬 수 있는 더 많은 DNA 수복 유전자의 다형성을 발굴하고 임상적으로 개인맞춤형 치료법을 개발하고 적용할 수 있는 많은 연구가 필요할 것으로 사료된다.

• 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.

• Animal cells and systems
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• 제9권2호
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• pp.79-85
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• 2005

Oxidized abasic residues arise as a major class of DNA damage by a variety of agents involving free radical attack and oxidation of deoxyribose sugar components. 2-deoxyribonolactone (dL) is a C1'-oxidized abasic lesion implicated in DNA strand scission, mutagenesis, and covalent DNA-protein cross-link (DPC). We show here that mammalian cell-free extract give rise to stable DPC formation that is specifically mediated by dL residue. When a duplex DNA containing dL at the site-specific position was incubated with cell-free extracts of Po ${\beta}-proficient$ and -deficient mouse embryonic fibroblast cells, the formation of major dL-mediated DPC was dependent on the presence of DNA polymerase (Pol) ${\beta}$. Formation of dL-specific DPC was also observed with histones and FEN1 nuclease, although the reactivity in forming dL-mediated DPC was significantly higher with Pol ${\beta}$ than with histones or FEN1. DNA repair assay with a defined DPC revealed that the dL lesion once cross-linked with Pol ${\beta}$ was resistant to nucleotide excision repair activity of cell-free extract. Analysis of nucleotide excision repair utilizing a model DNA substrate containing a (6-4) photoproduct suggested that excision process for DPC was inhibited because of DNA single-strand incision at 5' of the lesion. Consequently DPC mediated by dL lesion may not be readily repaired by DNA excision repair pathway but instead function as unusual DNA damage causing a prolonged DNA strand break and trapping of the major base excision repair enzyme.

• 대한의생명과학회지
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• 제11권2호
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• pp.103-108
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• 2005

2-Deoxyribonolactone (dL) arises as a major DNA damage induced by a variety of agents, involving free radical attack and oxidation of C1'-deoxyribose in DNA. We investigated whether dL lesions can be repaired in mammalian cells and the mechanisms underlying the role of DNA polymerase $\beta$ in processing of dL lesions. Pol $\beta$ appeared to be trapped by dL residues, resulting in stable DNA-protein cross-links. However, repair DNA synthesis at site-specific dL sites occurred effectively in cell-free extracts, but predominantly accompanied by long-patch base excision repair (BER) pathway. Reconstitution of long-patch BER demonstrated that FEN1 was capable of removing the displaced flap DNA containing a 5'-dL residue. Cellular repair of dL lesions was largely dependent on the DNA polymerase activity of Pol $\beta$. Our observations reveal repair mechanisms of dL and define how mammalian cells prevent cytotoxic effects of oxidative DNA lesions that may threaten the genetic integrity of DNA.

• 대한두개안면성형외과학회지
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• 제18권4호
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• pp.277-281
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• 2017

Traumatic cleft earlobes are a common problem encountered by plastic and reconstructive surgeons. Various techniques have been reported for the repair of traumatic cleft earlobes. Usually, the techniques of split earlobe repair are divided into two categories, namely straight- and broken-line repairs. Straight-line repair is simple and easy, but scar contracture frequently results in notching of the inferior border of the lobule. It can be avoided by the broken-line repair such as Z-plasty, L-plasty, or a V-shaped flap. Between April 2016 and February 2017, six patients who presented with traumatic cleft earlobe underwent surgical correction using a combination of the inverted V-shaped excision technique and vertical mattress suture method. All the patients were female and had a unilateral complete cleft earlobe. No postoperative notching of the inferior border the lobule occurred during 6-16 months of follow-up. Without the use of a broken-line repair, both the patients and the operators attained aesthetically satisfactory results. Therefore, the combination of the inverted V-shaped excision technique and vertical mattress suture method is considered useful in the treatment of traumatic cleft earlobes.

• 한국동물학회지
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• 제23권3호
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• pp.115-123
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• 1980

DNA 회복합성과 염색체이상과의 연관성여부를 추구하기 위하여 CHO 세포를 재료로 MNNG의 농도와 처리후 시간경과에 따른 절제회복율을 조사하고 이들 염색체 이상율과 비교하여 다음과 같은 결과를 얻었따. 1. MNNG에 의한 절제회복율은 $0.5 \\times 10^-5M$에서 $0.5 \\times 10^-5M$까지 농도의 증가에 따른 절제회복율의 증가를 보인다. 또 $1 \\times 10^-5M$ 처리후 0시간째는 절제회복율의 최고치를 보이다가 그후 점자 감소하여 24시간에는 0시간의 66%정도 나타난다. 2. MNNG에 의한 염색체이상은 $1 \\times 10^-5M$ 처리후 6시간에 최대치를 보이며 이상형의 대부분은 염색분체 절단을 나타낸다. 그러나 시간이 경과함에 따라 염색체분체절단은 감소하고 염색분체교환은 증가하여 24시간에는 두종류의 이상율이 비슷하게 이른다. 3. MNNG 처리후 시간경과에 따른 절제회복율은 전체이상율과 대체로 일치한다. 그러나 염색분체교환 또는 염색분체절단과는 어떤 비례관계도 보이지 않는다. 따라서 이같은 결과들은 MNNG에 의한 DNA 상해 및 그 회복은 염색체의 회복 현상과는 연관성이 없음을 암시하는 것이다.

• BMB Reports
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• 제49권10호
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• pp.566-571
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• 2016

Forskolin (FSK), an adenylyl cyclase activator, has recently been shown to enhance nucleotide excision repair (NER) upon UV exposure. However, our study revealed that this effect was detected in human skin epithelial ARPE19 cells only in growing cells, but not in non-cycling cells. When the cells were grown at low density (70% confluence), FSK was capable of stimulating cAMP responsive element binding (CREB) phosphorylation, a marker for FSK-stimulated PKA activation, and resulted in a significant increase of NER activity compared to control treatment. However, cells grown under 100% confluent conditions showed neither FSK-induced CREB phosphorylation nor the resulting NER enhancement. These findings indicate that cellular growth is critical for FSK-induced NER enhancement and suggest that cellular growth conditions should be considered as a variable while evaluating a reagent's pharmacotherapeutic efficacy.

• 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.

• Clinics in Shoulder and Elbow
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• 제21권4호
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• pp.234-239
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• 2018

Background: In elbow fracture-dislocation, partial excision of the comminuted radial head fracture that is not amenable to fixation remains controversial considering the accompanying symptoms. This study was undertaken to evaluate the results of radial head partial excision when the comminuted radial head fracture involved <50% of the articular surface in all-arthroscopic repair of elbow fracture-dislocation. Methods: Patients were divided into two groups based on the condition of the radial head fracture. In Group A, the patients had a radial head comminuted fracture involving <50% of the articular surface, and underwent arthroscopic partial excision. Group B was the non-excision group comprising patients with stable and non-displacement fractures. Follow-up consultations were conducted at 6 weeks and at 3, 6, 12, and 24 months after surgery. Results: In all, 19 patients (Group A: 11; Group B: 8) met the inclusion criteria and were enrolled in the study. At the final follow-up, all 19 patients showed complete resolution of elbow instability. No significant differences were observed in the range of motion, visual analogue scale score, and Mayo elbow performance score between groups. Radiological findings did not show any complications of the radiocapitellar joint. However, nonunion of the coracoid fracture was observed in 3 patients (Group A: 1; Group B: 2), without any accompanying instability and clinical symptoms. Conclusions: Considering that the final outcome is coronoid fracture fixation and lateral collateral ligament complex repair for restoring elbow stability, arthroscopic partial excision for radial head comminuted fractures involving <50% of articular surface is an effective and acceptable treatment for elbow fracture-dislocation.

• 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.