Department of Biochemistry and Molecular Medicine, the George Washington University School of Medicine and Health Sciences, Washington, DC 20037, USA.
GW Cancer Center, the George Washington University School of Medicine and Health Sciences, Washington, DC 20052, USA.
J Zhejiang Univ Sci B. 2021 Jan 15;22(1):47-62. doi: 10.1631/jzus.B2000344.
Alkylated DNA lesions, induced by both exogenous chemical agents and endogenous metabolites, represent a major form of DNA damage in cells. The repair of alkylation damage is critical in all cells because such damage is cytotoxic and potentially mutagenic. Alkylation chemotherapy is a major therapeutic modality for many tumors, underscoring the importance of the repair pathways in cancer cells. Several different pathways exist for alkylation repair, including base excision and nucleotide excision repair, direct reversal by methyl-guanine methyltransferase (MGMT), and dealkylation by the AlkB homolog (ALKBH) protein family. However, maintaining a proper balance between these pathways is crucial for the favorable response of an organism to alkylating agents. Here, we summarize the progress in the field of DNA alkylation lesion repair and describe the implications for cancer chemotherapy.
烷基化 DNA 损伤是由外源性化学试剂和内源性代谢物引起的，是细胞中 DNA 损伤的主要形式。烷基化损伤的修复在所有细胞中都至关重要，因为这种损伤具有细胞毒性和潜在的致突变性。烷基化化疗是许多肿瘤的主要治疗方式，这突显了修复途径在癌细胞中的重要性。有几种不同的途径可用于烷基化修复，包括碱基切除和核苷酸切除修复、甲基鸟嘌呤甲基转移酶 (MGMT) 的直接逆转，以及 AlkB 同源物 (ALKBH) 蛋白家族的脱烷基化。然而，在这些途径之间保持适当的平衡对于生物体对烷化剂的有利反应至关重要。在这里，我们总结了 DNA 烷基化损伤修复领域的进展，并描述了其对癌症化疗的影响。
