DNA alkylation lesion repair: outcomes and implications in cancer chemotherapy

DNA烷基化损伤修复及其在肿瘤化疗中的意义

Abstract

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.

概要

DNA烷基化损伤作为细胞内一种主要的DNA损伤形式,可由外源性化学试剂和内源性代谢物诱导发生。DNA烷基化损伤具有细胞毒性并可能诱导突变,因此烷基化损伤修 复在所有细胞内都至关重要。同时,烷基化肿瘤化学疗法是许多肿瘤的主要治疗方案,这也强调了癌细胞内烷基化修复途径的重要性。烷基化修复的途径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ALKBH蛋白家族的脱烷基化作用。然而,这些修复途径之间的内部平衡才是机体有效应答DNA烷基化试剂的关键所在。在这 里,我们总结了DNA烷基化损伤修复领域的进展,并进一步描述该领域的研究对肿瘤化疗的深刻意义。

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Yihan PENG wrote and edited the manuscript; Huadong PEI designed the study and revised the manuscript. Both authors have read and approved the final manuscript. Therefore, both authors have full access to the data in the study and take responsibility for the integrity and security of the data.

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Correspondence to Huadong Pei.

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Yihan PENG and Huadong PEI declare they have no conflict of interest.

This article does not contain any studies with human or animal subjects performed by either of the authors.

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Peng, Y., Pei, H. DNA alkylation lesion repair: outcomes and implications in cancer chemotherapy. J. Zhejiang Univ. Sci. B 22, 47–62 (2021). https://doi.org/10.1631/jzus.B2000344

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Key words

  • Alkylation repair
  • Base excision repair
  • Methyl-guanine methyltransferase (MGMT)
  • AlkB homolog (ALKBH)

关键词

  • DNA烷基化修复
  • 碱基切除修复
  • 甲基鸟嘌呤甲基转移酶(MGMT)
  • ALKBH