APExBIO -DNA Damage/DNA Repair系列產品+236
由於外部(exogenous, 外源性)和內部(endogenous, 內源性)壓力,人體細胞中的 DNA 每天會受到數以萬計的損害(damages)。外源性損害(exogenous damages)是由化學污染(chemical contamination)、紫外線(UV light)、電離輻射(ionizing radiation)和烷基化/甲基化(alkylation/methylation)等引起的,而內源性損害(endogenous damages)是由鹼的氧化(oxidation)、烷基化(alkylation)和水解(hydrolysis)等引起的。由於DNA損傷(double strand breaks)後會發生單鍊(single strand)和雙鏈斷裂(double strand breaks),未修復的DNA損傷導致細胞衰老(cell senescent)、凋亡(apoptosis)和惡性腫瘤(malignancies)等。為了克服這種威脅,細胞產生了 DNA 損傷反應(DNA damage response),以檢測 DNA 損傷並介導其修復(repair)。DNA修復涉及錯配、鹼基切除、核苷酸切除修復等多種機制。一組蛋白質和途徑參與了這些過程。 ATM/ATR 激酶和 DNA-PK 對於檢測 DNA 損傷至關重要。染色質重塑劑調節 DNA 修復因子發揮作用的染色質可及性。 RPA、Rad51 和範可尼貧血蛋白直接作用於修復 DNA 損傷。 p53 網絡、RAS GTPase 超家族和泛素系統也在 DNA 損傷反應中發揮重要作用。異常的 DNA 損傷反應與衰老、癌症和免疫疾病有關。
The DNA in a human cell receives tens of thousands of damages per day due to both external (exogenous) and internal (endogenous) stress. The exogenous damages are caused by chemical contamination, UV light, ionizing radiation and alkylation/methylation etc, while the endogenous damages are coming from oxidation, alkylation and hydrolysis of bases etc. Since single strand and double strand breaks of DNA will occur after the damage, unrepaired DNA damage leads to cell senescent, apoptosis and malignancies etc. To overcome this threat, cell has developed DNA damage response, to detect DNA damage and mediate its repair.
DNA repair involves multiple mechanisms such as mismatch, base excision, and nucleotide excision repair etc. A group of proteins and pathways are participated in those processes. ATM/ATR kinases and DNA-PK are crucial for the detection of the DNA damage. Chromatin remodelers regulate chromatin accessibility for the DNA repair factors to function. RPA, Rad51 and the fanconi anemia proteins act directly on repairing the DNA damage. p53 network, the RAS GTPase superfamily, and the ubiquitin system also play important part in the DNA damage response. Aberrant DNA damage response is linked to aging, cancer and immune diseases.
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