Laboratory of Laboratory Animal Science, Graduate School of Life and Environmental Biosciences, Osaka Prefecture University, Izumisano, Osaka, Japan.
The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
DNA Repair (Amst). 2020 Apr;88:102806. doi: 10.1016/j.dnarep.2020.102806. Epub 2020 Feb 10.
Covalent binding between proteins and a DNA strand produces DNA-protein crosslinks (DPC). DPC are one of the most deleterious types of DNA damage, leading to the blockage of DNA replication and transcription. Both DNA lesions and endogenous products with carbonyl functional groups can produce DPC in genomic DNA under normal physiological conditions. For example, formaldehyde, the most abundant endogenous human carcinogen, and apurinic/apyrimidinic (AP) sites, the most common type of endogenous DNA lesions, has been shown to crosslink proteins and/or DNA through their carbonyl functional groups. Unfortunately, compared to other types of DNA damage, DPC have been less studied and understood. However, a recent advancement has allowed researchers to determine accurate yields of various DNA lesions including formaldehyde-derived DPC with high sensitivity and specificity, paving the way for new developments in this field of research. Here, we review the current literature and remaining unanswered questions on DPC formation by endogenous formaldehyde and various aldehydic 2-deoxyribose lesions.
蛋白质与 DNA 链之间的共价结合会产生 DNA-蛋白质交联（DPC）。DPC 是最具危害性的 DNA 损伤类型之一，会导致 DNA 复制和转录受阻。在正常生理条件下，DNA 损伤和具有羰基官能团的内源性产物都可能在基因组 DNA 中产生 DPC。例如，甲醛是最丰富的内源性人类致癌物，而无嘌呤/无嘧啶（AP）位点是最常见的内源性 DNA 损伤类型，已被证明可以通过其羰基官能团将蛋白质和/或 DNA 交联。不幸的是，与其他类型的 DNA 损伤相比，DPC 的研究和理解较少。然而，最近的一项进展使得研究人员能够以高灵敏度和特异性来确定各种 DNA 损伤（包括甲醛衍生的 DPC）的确切产量，为该研究领域的新发展铺平了道路。在这里，我们综述了内源性甲醛和各种醛脱氧核糖损伤形成 DPC 的现有文献和未解决的问题。
