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

Consensus ; DNA Repair ; Humans ; Male ; Prostatic Neoplasms/genetics* ; Recombinational DNA Repair

Cerebellar Neoplasms ; genetics ; DNA Repair ; Humans ; Medulloblastoma ; genetics

Brain Neoplasms ; pathology ; physiopathology ; DNA Repair ; genetics ; Glioma ; pathology ; physiopathology ; Humans ; Statistics as Topic ; Targeted Gene Repair

DNA End-Joining Repair ; Humans ; Immunologic Deficiency Syndromes ; genetics

OBJECTIVETo investigate the potential substitution effect of hOGG1 and hMTH1 on oxidative DNA damage, based on gene-deficient cell strains models.

METHODShOGG1 and hMTH1 gene deficient cell strains models were established by Human embryonic lung fibroblasts (HFL) cells. After HFL cells being exposed to 100 µmol/L H₂O₂ for 12 h, HPLC-EC detecting technique and RT-PCR method were adopted to analyze the genetic expression level of 8-oxo-dG (7, 8-dihydro-8-oxoguanine).

RESULTSThe gene-deficient cell strains models of hOGG1 and hMTH1 were obtained by infecting target cells with high titer of lentivirus. The mRNA expression level of hOGG1 was 0.09 ± 0.02, 91% lower than it in normal HFL cells, which was 1.00 ± 0.04. As the same, the mRNA expression level of hMTH1 (0.41 ± 0.04) also decreased by 60% compared with it in normal HFL cells (1.02 ± 0.06). After induced by 100 µmol/L H₂O₂ for 12 h, the genetic expression level of hMTH1 in hOGG1 gene-deficient cells (1.26 ± 0.18) increased 25% compared with it in control group (1.01 ± 0.07). Meanwhile, the genetic expression level of hOGG1 in hMTH1 gene-deficient cells (1.54 ± 0.25) also increased by 52%. The DNA 8-oxo-dG levels in hOGG1 gene-deficient cells (2.48 ± 0.54) was 3.1 times compared with it in the control group (0.80 ± 0.16), the difference showed statistical significance (P < 0.01). Whereas the 8-oxo-dG levels in hMTH1 gene-deficient cells (1.84 ± 0.46) was 2.3 times of it in the control group, the difference also showed statistical significance (P < 0.01).

CONCLUSIONBased on gene-deficient HFL cells models, a synergetic substitution effect on DNA damage and repair activity by both hOGG1 and hMTH1 were firstly discovered when induced by oxidation. The substitution effect of hOGG1 were stronger than that of hMTH1.

Cell Line ; DNA Damage ; DNA Glycosylases ; genetics ; DNA Repair ; DNA Repair Enzymes ; genetics ; Fibroblasts ; metabolism ; Humans ; Oxidative Stress ; genetics ; Phosphoric Monoester Hydrolases ; genetics

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

As novel somatic mutations, spliceosome mutations have been identified in recent years with the advent of whole exone/genome sequencing technology in hematopoietic malignancy. These new findings provide another view to understand these diseases other than DNA methylation, chromatin modification, transcription regulation, DNA repair and signal transduction. In this review, the structure as well as function of spliceosome are introduced and the common mutations such as SF3B1, U2AF35, SRSF2 and ZRSR2 as well as their frequency, mutation versions, clinical phenotypies and effects on prognosis are discussed.
DNA Methylation ; DNA Repair ; Hematologic Neoplasms ; genetics ; Humans ; Mutation ; Myelodysplastic Syndromes ; Prognosis ; Signal Transduction ; Spliceosomes ; genetics

Prostate cancer is one of the most common malignant tumors in males, and its etiology and pathogenesis remain unclear. Epigenesis is involved in prostate cancer at all stages of the process, and closely related with its growth and metastasis. DNA methylation and histone modification are the most important manifestations of epigenetics in prostate cancer. The mechanisms of carcinogenesis of DNA methylation include whole-genome hypomethylation, aberrant local hypermethylation of promoters and genomic instability. DNA methylation is closely related to the process of prostate cancer, as in DNA damage repair, hormone response, tumor cell invasion/metastasis, cell cycle regulation, and so on. Histone modification causes corresponding changes in chromosome structure and the level of gene transcription, and it may affect the cycle, differentiation and apoptosis of cells, resulting in prostate cancer. Some therapies have been developed targeting the epigenetic changes in prostate cancer, including DNA methyltransferases and histone deacetylase inhibitors, and have achieved certain desirable results.
DNA Methylation ; DNA Repair ; Epigenesis, Genetic ; Epigenomics ; Histones ; genetics ; Humans ; Male ; Prostatic Neoplasms ; genetics

Apoptosis ; genetics ; DNA Repair ; DNA-(Apurinic or Apyrimidinic Site) Lyase ; chemistry ; genetics ; physiology ; Humans