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首页> 外文期刊>Twin research and human genetics : >Plenary 8: GENOMIC INSTABILITY: SENSING DNA DAMAGE
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Plenary 8: GENOMIC INSTABILITY: SENSING DNA DAMAGE

机译：全体列8：基因组不稳定性：感测DNA损伤

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Introduction: DNA damage is the underlying cause of cellular aging and diseases of age such as cancer and neuro-degeneration. The cell posesses a large number of proteins that function to detect, signal, and repair specific DNA lesions within the genome. One such protein, hSSB1, functions to detect double-strand DNA breaks. One critical pathway responsible for the removal of oxidized nucleotides from the genome is the Base Excision Repair pathway (BER). This relatively simple pathway requires a DNA glycosylase to excise the base and an AP nuclease to cleave the phosphate backbone, allowing the incorporation of the correct nucleotide. Results: It was previously thought that 8-oxoG lesions (the most commonly oxidized nucleotide) were detected by the DNA glycosylase hOGG1; however, our data now indicates that hSSB1 is the cellular sensor of 8-oxoG containing double-stranded DNA. hSSB 1 binds to duplex DNA containing 8-oxoG with high affinity and recruits the DNA glycosylase hOGG1 to the site of damage. hSSB1 further stimulates the activity of hOGG1, allowing the removal of the base. Interestingly, hSSB1 has an oxidation-sensing cysteine (C81) that detects oxidized conditions and stimulates dimerization of hSSB1, with this event being required for recognition of the 8-oxoG lesion but not DNA double-strand breaks. Conclusions: We have now identified the sensor of oxidized guanines nucelotides within the genome. hSSB1 is over-expressed in most solid malignancies and may function to allow the cell to tolerate high levels of 8-oxoG generation. This could make hSSB1 an attractive drug target.
机译：介绍：DNA损伤是细胞老化和年龄疾病如癌症和神经变性的潜在原因。细胞停滞大量蛋白质，其功能用于检测，信号和修复基因组内的特异性DNA病变。一种这样的蛋白质，HSSB1，用于检测双链DNA断裂的功能。负责从基因组去除氧化核苷酸的一种关键途径是基础切除修复途径（BER）。该相对简单的途径需要DNA糖基酶以切除碱和AP核酸酶以切割磷酸盐骨架，从而掺入正确的核苷酸。结果：先前认为，DNA糖基酶术术术检测8-氧代病变（最常见的氧化核苷酸）;然而，我们的数据现在表明HSSB1是含有双链DNA的8-氧的蜂窝传感器。 HSSB 1与具有高亲和力的8- Oxog的双链DNA结合，并将DNA糖基酶Hogg1促进到损伤部位。 HSSB1进一步刺激霍格1的活性，允许去除碱基。有趣的是，HSSB1具有氧化感测的半胱氨酸（C81），其检测氧化条件并刺激HSSB1的二聚化，并且这种事件被要求识别8-氧代病变，但不是DNA双链断裂。结论：我们现在已经确定了基因组内氧化的鸟嘌呤Nucelotes的传感器。 HSSB1以大多数固体恶性肿瘤过度表达，并且可以使细胞能够容忍高水平的8氧代生成。这可能使HSSB1成为一种有吸引力的药物目标。

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