Role of C. elegans AP endonuclease, APN-1, in removing DNA lesions generated through transporter-mediated uptake of naturally occurring toxic compounds.

线虫 AP 核酸内切酶 (APN-1) 在消除转运蛋白介导的天然有毒化合物摄取产生的 DNA 损伤中的作用。

• 批准号: RGPIN-2017-04244
• 负责人: Ramotar, Dindial
• 金额: $ 2.48万
• 依托单位: Université de Montréal
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=629206
• 关键词: Role; C.; elegans; AP; endonuclease

Damage to the DNA can occur naturally by endogenous agents such as reactive oxygen species, and by several exogenous agents such as polycyclic aromatic compounds and oxidized metabolites. These agents can create hundreds of distinct DNA lesions including oxidative base damage that can undergo further structural changes to give rise to even more toxic DNA lesions. If these DNA lesions are not repaired, they can alter the genome to cause cell death and thus lead to many age related diseases. To avoid these deleterious effects, there are several pathways that act to remove specific classes of DNA lesions. Since 1993, we have been focusing on the base-excision DNA repair pathway that acts to remove oxidative DNA lesions. This pathway is made up of several enzymatic steps involving the recognition of the oxidative DNA lesions, removing the lesions, and restoring the DNA sequence to normal; our focus was mostly on the second step. In this step, following removal of the damage base by DNA glycosylase, the resulting apurinic/apyrimidinic (AP) site is cleaved by an AP endonuclease to initiate DNA repair synthesis. There are two distinct families of AP endonucleases, exemplified by

对DNA的损伤可以通过内源性试剂如活性氧物质和几种外源性试剂如多环芳族化合物和氧化代谢物自然发生。这些试剂可以产生数百种不同的DNA损伤，包括氧化性碱基损伤，这些损伤可以经历进一步的结构变化，从而产生更具毒性的DNA损伤。如果这些DNA损伤得不到修复，它们可能会改变基因组，导致细胞死亡，从而导致许多与年龄相关的疾病。为了避免这些有害影响，有几种途径可以消除特定类型的DNA损伤。自1993年以来，我们一直专注于碱基切除DNA修复途径，其作用是去除氧化DNA损伤。该途径由几个酶促步骤组成，涉及识别氧化DNA损伤，去除损伤，并将DNA序列恢复正常;我们的重点主要是第二步。在该步骤中，在通过DNA糖基化酶去除损伤碱基之后，所得脱嘌呤/脱嘧啶（AP）位点被AP内切核酸酶切割以启动DNA修复合成。存在两个不同的AP核酸内切酶家族，例如