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DNA-protein crosslink formation by endogenous aldehydes and AP sites.
DNA Repair ( IF 3.0 ) Pub Date : 2020-02-10 , DOI: 10.1016/j.dnarep.2020.102806
Jun Nakamura 1 , Mai Nakamura 2
Affiliation  

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.

中文翻译:

DNA-蛋白质交联通过内源性醛和AP位点形成。

蛋白质和DNA链之间的共价结合会产生DNA-蛋白质交联(DPC)。DPC是最有害的DNA损伤类型之一,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均可在基因组DNA中产生DPC。例如,已显示甲醛(最丰富的内源性人类致癌物)和嘌呤/嘧啶(AP)位点(最常见的内源性DNA损伤类型)通过蛋白质的羰基官能团交联蛋白质和/或DNA。不幸的是,与其他类型的DNA损伤相比,对DPC的研究和了解较少。然而,最近的进展使研究人员能够以高灵敏度和特异性确定各种DNA损伤的准确产量,包括甲醛衍生的DPC,这为该研究领域的新发展铺平了道路。在这里,我们回顾了有关内源性甲醛和各种醛基2-脱氧核糖病形成DPC的最新文献和尚待解决的问题。
更新日期:2020-02-10
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