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

DNA 损伤可由内源性物质（如活性氧）和多种外源性物质（如多环芳香族化合物和氧化代谢物）自然发生。这些药物可以产生数百种不同的 DNA 损伤，包括氧化碱基损伤，氧化碱基损伤可以发生进一步的结构变化，从而产生更具毒性的 DNA 损伤。如果这些 DNA 损伤得不到修复，它们就会改变基因组，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别的 DNA 损伤。自 1993 年以来，我们一直专注于碱基切除 DNA 修复途径，该途径可消除氧化性 DNA 损伤。该途径由几个酶促步骤组成，包括识别氧化性 DNA 损伤、去除损伤以及将 DNA 序列恢复正常；我们的重点主要集中在第二步上。在此步骤中，在 DNA 糖基化酶去除损伤碱基后，产生的脱嘌呤/脱嘧啶 (AP) 位点被 AP 核酸内切酶切割，以启动 DNA 修复合成。 AP 核酸内切酶有两个不同的家族，例如