DNA ; DNA Damage ; DNA Repair ; Fanconi Anemia/genetics* ; Humans

Benzene ; poisoning ; DNA Damage ; DNA Repair ; genetics ; Deoxyguanosine ; analogs & derivatives ; genetics ; Humans ; Mutagens ; poisoning ; Poisoning ; genetics

OBJECTIVE: To explore the change rules of peak area ratio of STR loci to Amelogenin (AMEL) locus (STR/AMEL), a sex-determining gene in DNA degradation, and to evaluate the application of STR/AMEL value in the estimation of DNA degradation degree. METHODS: DNA was extracted from iliopsoas, and the variations of STR/AMEL value (Penta E/AMEL, Penta D/AMEL, FGA/AMEL) were analyzed after the artificial degradation was made by DNase I, and the changes of these three ratios of the iliopsoas naturally degraded in an outdoor environment were also analyzed. The regression curves were analyzed using the periods of DNA degradation and outside the body as the independent variable (x) and the STR/AMEL value as the dependent variable (y) and three curve equations under two conditions were established. RESULTS: Both under the conditions of artificial and natural degradation, STR/AMEL value had a negative relationship with the degradation time. The relationship between STR/AMEL and degradation time can be well simulated by the cubic function. R2 was over 0.99 under controlled degradation condition and over 0.86 under natural degradation condition. CONCLUSION The STR/AMEL value (Penta E/AMEL, Penta D/AMEL, FGA/AMEL) is negatively related with the DNA degradation degree, which follows mathematical regression models strictly, and it might be applied to evaluate the DNA degradation degree.
Amelogenin/genetics* ; DNA Damage/genetics* ; DNA Primers ; Humans ; Microsatellite Repeats ; Regression Analysis ; Time Factors

DNA Damage ; DNA Glycosylases ; genetics ; metabolism ; DNA Repair Enzymes ; genetics ; metabolism ; Humans ; Phosphoric Monoester Hydrolases ; genetics ; metabolism

Fanconi anemia (FA) is a rare genetic disease with both autosomal and X-linked inheritance, characterized by genomic instability. The cells from individuals with FA are highly sensitive to DNA-crosslinking drugs, such as mitomycin C (MMC), diepoxybutane (DEB) and so on. Now at least 13 genes (FA-A, B, C, D1, D2, E, F, G, I, J, L, M, N) have been identified, whose products participate in a DNA damage-response network involving breast cancer susceptibility gene products, BRCA1 and BRCA2. The impaired DNA repair due to mutations in FA genes is thought to be one of the main pathogenesis of FA, also closely related to the development of some cancers. In this review, the advances of study about FA-BRCA network are summarized.
DNA Damage ; DNA Repair ; Fanconi Anemia ; genetics ; pathology ; Genes, BRCA2 ; Humans

OBJECTIVETo evaluate and compare standard sperm parameters and sperm DNA fragmentation in seminal ejaculates from men whose partners had a history of recurrent pregnancy loss (RPL) and a control group of men who had recently established their fertility.

METHODSSemen samples from 85 patients with a history of RPL and 20 men with proven fertility were analyzed according to World Health Organization guidelines. Sperm DNA fragmentation was detected by sperm chromatin dispersion test (SCD).

RESULTSA significant difference (P< 0.05) was observed in sperm motility but not other parameters between the two groups. The mean number of sperm cells with fragmented DNA, represented as DNA fragmentation index, was significantly increased in the RPL group [(34.99± 14.62)%] compared with controls [(10.82± 4.80)%].

CONCLUSIONThis study has indicated that sperm from men with a history of RPL have a higher incidence of DNA damage and poor motility compared with fertile males.

Abortion, Habitual ; etiology ; genetics ; Adult ; DNA Damage ; DNA Fragmentation ; Female ; Humans ; Male ; Pregnancy ; Sperm Motility

DNA damage repair (DDR) system plays an important role in maintaining of genomic stability. Accumulation of DNA lesions or deficiency of DDR system could drive tumorigenesis as well as promote tumor progression; meanwhile, they could also provide therapeutic opportunities and targets. Of all the antineoplastic agents of lung cancers, many of them targeted or were associated with DNA damage and repair pathways, such as chemotherapies and antibody-drug conjugates which were designed directly causing DNA damages, targeted drugs inhibiting DNA repair pathways, and immune-checkpoint inhibitors. In this review, we described the role of DNA damage and repair pathways in antitumor activity of the above agents, as well as summarized the application and clinical investigations of these antineoplastic agents in lung cancers, in order to provide more information for exploring precision and effective strategies for the treatment of lung cancer based on the mechanism of DNA damage and repair.
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Antineoplastic Agents/therapeutic use* ; DNA Damage ; DNA Repair ; Humans ; Lung Neoplasms/genetics* ; Neoplasms/drug therapy*

OBJECTIVES: To investigate the effects and mechanisms of deubiquitinating enzyme Josephin domain containing 2 (JOSD2) on susceptibility of non-small cell lung carcinoma (NSCLC) cells to anti-cancer drugs. METHODS: The transcriptome expression and clinical data of NSCLC were downloaded from the Gene Expression Omnibus. Principal component analysis and limma analysis were used to investigate the deubiquitinating enzymes up-regulated in NSCLC tissues. Kaplan-Meier analysis was used to investigate the relationship between the expression of deubiquitinating enzymes and overall survival of NSCLC patients. Gene ontology enrichment and gene set enrichment analysis (GSEA) were used to analyze the activation of signaling pathways in NSCLC patients with high expression of JOSD2. Gene set variation analysis and Pearson correlation were used to investigate the correlation between JOSD2 expression levels and DNA damage response (DDR) pathway. Western blotting was performed to examine the expression levels of JOSD2 and proteins associated with the DDR pathway. Immunofluorescence was used to detect the localization of JOSD2. Sulforhodamine B staining was used to examine the sensitivity of JOSD2-knock-down NSCLC cells to DNA damaging drugs. RESULTS: Compared with adjacent tissues, the expression level of JOSD2 was significantly up-regulated in NSCLC tissues (P<0.05), and was significantly correlated with the prognosis in NSCLC patients (P<0.05). Compared with the tissues with low expression of JOSD2, the DDR-related pathways were significantly upregulated in NSCLC tissues with high expression of JOSD2 (all P<0.05). In addition, the expression of JOSD2 was positively correlated with the activation of DDR-related pathways (all P<0.01). Compared with the control group, overexpression of JOSD2 significantly promoted the DDR in NSCLC cells. In addition, DNA damaging agents significantly increase the nuclear localization of JOSD2, whereas depletion of JOSD2 significantly enhanced the sensitivity of NSCLC cells to DNA damaging agents (all P<0.05). CONCLUSIONS Deubiquitinating enzyme JOSD2 may regulate the malignant progression of NSCLC by promoting DNA damage repair pathway, and depletion of JOSD2 significantly enhances the sensitivity of NSCLC cells to DNA damaging agents.
Humans ; Carcinoma, Non-Small-Cell Lung/genetics* ; Antineoplastic Agents/pharmacology* ; Lung Neoplasms/genetics* ; DNA Damage ; DNA ; Deubiquitinating Enzymes/genetics*

Human sperm chromatin damage is one of the common reasons for reduced male reproductive capacity, which is influenced by genetics, environment, lifestyle and other factors, as well as associated with male infertility and habitual abortion. Along with deeper insights into the structure and function of sperm chromatin, improvement and promotion of detection technology for its integrity, and wider application of assisted reproductive technology, sperm DNA damage has been recognized as an important new indicator for the evaluation of sperm quality, and has a great clinical significance in the assessment of male fertility and selection of assisted reproductive technology.
Chromatin ; genetics ; DNA Damage ; Humans ; Infertility, Male ; genetics ; Male ; Reproductive Techniques, Assisted ; Spermatozoa

p53 is considered as the "master regulator" in DNA damage-induced cell apoptosis. However, p53 is the most frequently mutated gene in human cancers (more than 50 %). Thus the research of p53-independent pathway in cell apoptosis may ultimately provide new therapeutic opportunities for many cancers. It has been shown that Caspase 2, p73, p63, and NF-kappa B-related signaling pathways are involved in DNA damage-induced, p53-independent cell apoptosis. This article reviews the recent research progress in these signaling pathways.
Apoptosis ; genetics ; DNA Damage ; Humans ; Signal Transduction ; Tumor Suppressor Protein p53 ; genetics ; metabolism