Department of Molecular Biology, Skaggs Institute for Chemical Biology, La Jolla, CA 92037, USA.
Cell Mol Life Sci. 2010 Nov;67(22):3749-62. doi: 10.1007/s00018-010-0405-8. Epub 2010 May 26.
Alkyltransferase-like proteins (ATLs) play a role in the protection of cells from the biological effects of DNA alkylation damage. Although ATLs share functional motifs with the DNA repair protein and cancer chemotherapy target O⁶-alkylguanine-DNA alkyltransferase, they lack the reactive cysteine residue required for alkyltransferase activity, so its mechanism for cell protection was previously unknown. Here we review recent advances in unraveling the enigmatic cellular protection provided by ATLs against the deleterious effects of DNA alkylation damage. We discuss exciting new evidence that ATLs aid in the repair of DNA O⁶-alkylguanine lesions through a novel repair cross-talk between DNA-alkylation base damage responses and the DNA nucleotide excision repair pathway.
烷基转移酶样蛋白 (ATLs) 在保护细胞免受 DNA 烷基化损伤的生物学效应方面发挥作用。尽管 ATLs 与 DNA 修复蛋白和癌症化疗靶标 O⁶-烷基鸟嘌呤-DNA 烷基转移酶具有功能基序,但它们缺乏烷基转移酶活性所需的反应性半胱氨酸残基,因此其细胞保护机制以前是未知的。在这里,我们回顾了最近在揭示 ATLs 对 DNA 烷基化损伤的有害影响提供的神秘细胞保护方面的进展。我们讨论了令人兴奋的新证据,即 ATLs 通过 DNA-烷基化碱基损伤反应与 DNA 核苷酸切除修复途径之间的新的修复交叉对话,有助于修复 DNA O⁶-烷基鸟嘌呤损伤。