DNA Oxidation and Excision Repair Pathways

Lee, Tae-Hee; Kang, Tae-Hong

doi:10.3390/ijms20236092

Cited by 74 publications

(60 citation statements)

References 83 publications

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“…On the other hand, mitochondrial dysfunction in MGRN1-KO cells likely augments the production of reactive oxygen species (ROS), leading to higher oxidative stress [ 7 ]. In DNA, ROS predominantly damage bases or deoxirribose, with 8-oxo-7,8-dihydroguanine (8-oxodG) as the main oxidation product [ 44 ]. We compared the levels of 8-oxodG in melan-a6 and Mgrn1 -KO clones.…”

Section: Resultsmentioning

confidence: 99%

Mahogunin Ring Finger 1 Is Required for Genomic Stability and Modulates the Malignant Phenotype of Melanoma Cells

Martínez-Vicente

Abrisqueta

Herráiz

et al. 2020

Cancers

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The mouse mahoganoid mutation abrogating Mahogunin Ring Finger-1 (MGRN1) E3 ubiquitin ligase expression causes hyperpigmentation, congenital heart defects and neurodegeneration. To study the pathophysiology of MGRN1 loss, we compared Mgrn1-knockout melanocytes with genetically matched controls and melan-md1 (mahoganoid) melanocytes. MGRN1 knockout induced a more differentiated and adherent phenotype, decreased motility, increased the percentage of cells in the S phase of the cell cycle and promoted genomic instability, as shown by stronger γH2AX labelling, increased burden of DNA breaks and higher abundance of aneuploid cells. Lack of MGRN1 expression decreased the ability of melanocytes to cope with DNA breaks generated by oxidizing agents or hydroxyurea-induced replicative stress, suggesting a contribution of genomic instability to the mahoganoid phenotype. MGRN1 knockout in B16-F10 melanoma cells also augmented pigmentation, increased cell adhesion to collagen, impaired 2D and 3D motility and caused genomic instability. Tumors formed by Mgrn1-KO B16-F10 cells had lower mitotic indices, fewer Ki67-positive cells and showed a trend towards smaller size. In short-term lung colonization assays Mgrn1-KO cells showed impaired colonization potential. Moreover, lower expression of MGRN1 is significantly associated with better survival of human melanoma patients. Therefore, MGRN1 might be an important phenotypic determinant of melanoma cells.

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Section: Resultsmentioning

confidence: 99%

Mahogunin Ring Finger 1 Is Required for Genomic Stability and Modulates the Malignant Phenotype of Melanoma Cells

Martínez-Vicente

Abrisqueta

Herráiz

et al. 2020

Cancers

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“…No statistical significance was found in BER-DRC based on the pathologic stage of the tumors and the expression levels of BER genes did not correlate with BER-DRC [86]. Current reports suggest that oxidative DNA damage may be removed from DNA also via NER [87,88] and the authors postulate that loss of NER function shares common features arising from BER defects, including cancer predisposition [89]. Despite we have recorded significantly higher NER DRC in tumor tissue from CRC patients in comparison to adjacent mucosa, we fail to ascribe this change to any specific DNA damage [86].…”

Section: Base Excision Repair Capacity In Sporadic Colorectal Cancermentioning

confidence: 92%

Oxidative Damage in Sporadic Colorectal Cancer: Molecular Mapping of Base Excision Repair Glycosylases in Colorectal Cancer Patients

Vodička

Urbanová

Makovický

et al. 2020

IJMS

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Oxidative stress with subsequent premutagenic oxidative DNA damage has been implicated in colorectal carcinogenesis. The repair of oxidative DNA damage is initiated by lesion-specific DNA glycosylases (hOGG1, NTH1, MUTYH). The direct evidence of the role of oxidative DNA damage and its repair is proven by hereditary syndromes (MUTYH-associated polyposis, NTHL1-associated tumor syndrome), where germline mutations cause loss-of-function in glycosylases of base excision repair, thus enabling the accumulation of oxidative DNA damage and leading to the adenoma-colorectal cancer transition. Unrepaired oxidative DNA damage often results in G:C>T:A mutations in tumor suppressor genes and proto-oncogenes and widespread occurrence of chromosomal copy-neutral loss of heterozygosity. However, the situation is more complicated in complex and heterogeneous disease, such as sporadic colorectal cancer. Here we summarized our current knowledge of the role of oxidative DNA damage and its repair on the onset, prognosis and treatment of sporadic colorectal cancer. Molecular and histological tumor heterogeneity was considered. Our study has also suggested an additional important source of oxidative DNA damage due to intestinal dysbiosis. The roles of base excision repair glycosylases (hOGG1, MUTYH) in tumor and adjacent mucosa tissues of colorectal cancer patients, particularly in the interplay with other factors (especially microenvironment), deserve further attention. Base excision repair characteristics determined in colorectal cancer tissues reflect, rather, a disease prognosis. Finally, we discuss the role of DNA repair in the treatment of colon cancer, since acquired or inherited defects in DNA repair pathways can be effectively used in therapy.

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“…Studies on the molecular mechanisms of the susceptibility to cutaneous malignant melanoma genes have suggested that this susceptibility is associated with sequence variation mutations in NER genes ( 2 , 24 ). Mutated XPD may be a biomarker of skin malignant melanoma ( 1 ). Kertat et al ( 25 ) revealed that the Gln/Gln genotype of the XPD 751 codon is a genetic marker of male malignant melanoma, and that the Lys/Gln genotype is important for predicting tumor progression.…”

Section: Discussionmentioning

confidence: 99%

“…UV radiation, smoking and various other environmental factors can cause DNA damage (1). In the human body, DNA damage can be corrected by direct repair, base excision repair and nucleotide excision repair (NER) to maintain genome stability.…”

Section: Introductionmentioning

confidence: 99%

“…In the human body, DNA damage can be corrected by direct repair, base excision repair and nucleotide excision repair (NER) to maintain genome stability. Among these, the NER system is the primary repair method (1). If DNA damage is not removed or repaired in time, it can lead to various diseases, such as cancer and neurodegenerative diseases, Parkinson's disease, Alzheimer's disease, Huntington's disease, aging (2).…”

Section: Introductionmentioning

confidence: 99%

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Cloning of the XPD gene and its function in malignant melanoma cells

et al. 2020

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The xeroderma pigmentosum group D (XPD) gene is a member of the transcription factor IIH complex and serves an important role in gene repair. Previous studies have suggested that genetic variants of the XPD gene may be associated with an increased risk of cutaneous melanoma. However, the exact mechanism remains unclear. In the present study, the XPD gene was cloned, and its localization and function in malignant melanoma cells were investigated. The human full length XPD gene was cloned via reverse transcription-PCR using the total RNA extracted from human cervical squamous cell carcinoma epithelial HeLa cells. Subsequently, the gene was inserted into a plasmid fused to green fluorescent protein (GFP; pEGFP-N1/XPD), and pEGFP-N1/XPD and pcDNA3.1(+)/XPD were transfected into human malignant melanoma A375 cells using Lipofectamine ® 2000. The expression levels of XPD were detected by western blotting. The Golgi marker GM130 and the endoplasmic reticulum membrane protein marker KDEL were used for immunofluorescence staining, and the subcellular localization of XPD was observed under a fluorescence microscope. Cell proliferation was measured using an MTT assay. The recombinant pEGFP-N1/XPD plasmid expressing the human wild-type XPD gene was successfully constructed by restriction enzyme digestion and assessed by gene sequencing. XPD was localized in the endoplasmic reticulum of malignant melanoma A375 cells, as confirmed by immunofluorescence staining. Furthermore, MTT assays indicated that XPD inhibited the proliferation of malignant melanoma A375 cells. The present study provides a basis for further investigation of the biological effects and functions of XPD in malignant melanoma cells.

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DNA Oxidation and Excision Repair Pathways

Cited by 74 publications

References 83 publications

Mahogunin Ring Finger 1 Is Required for Genomic Stability and Modulates the Malignant Phenotype of Melanoma Cells

Mahogunin Ring Finger 1 Is Required for Genomic Stability and Modulates the Malignant Phenotype of Melanoma Cells

Oxidative Damage in Sporadic Colorectal Cancer: Molecular Mapping of Base Excision Repair Glycosylases in Colorectal Cancer Patients

Cloning of the XPD gene and its function in malignant melanoma cells

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