The aim of this review is to describe the reactions which lead to generation of 5-hydroxymethyluracil, as well as the repair processes involved in its removal from DNA, and its level in various cells and urine. 5-hydroxymethyluracil may be formed during the course of the two processes: oxidation/hydroxylation of thymine with resultant formation of 5-hydroxymethyluracil paired with adenine (produced by reactive oxygen species), and reacting of reactive oxygen species with 5-methylcytosine forming 5-hydroxymethylcytosine, followed by its deamination to 5-hydroxymethyluracil mispaired with guanine. However, other, perhaps enzymatic, mechanism(s) may be involved in formation of 5-hydroxymethyluracil mispaired with guanine. Indeed, this mispair may be also formed as a result of deamination of 5-hydroxymethylcytosine, recently described "sixth" DNA base. It was demonstrated that 5-hydroxymethyluracil paired with adenine can be also generated by TET enzymes from thymine during mouse embryonic cell differentiation. Therefore, it is possible that 5-hydroxymethyluracil is epigenetic mark. The level of 5-hydroxymethyluracil in various somatic tissues is relatively stable and resembles that observed in lymphocytes, about 0.5/10(6) dN in human colon, colorectal cancer as well as various rat and porcine tissues. Experimental evidence suggests that SMUG1 and TDG are main enzymes involved in removal of 5-hydroxymethyluracil from DNA. 5-hydroxymethyluracil, in form of 5-hydroxymethyluridine, was also detected in rRNA, and together with SMUG1 may play a role in rRNA quality control. To summarize, 5-hydroxymethyluracil is with no doubt a product of both enzymatic and reactive oxygen species-induced reaction. This modification may probably serve as an epigenetic mark, providing additional layer of information encoded within the genome. However, the pool of 5-hydroxymethyluracil generated as a result of oxidative stress is also likely to disturb physiological epigenetic processes, and as such may be defined as a lesion. Altogether this suggests that 5-hydroxymethyluracil may be either a regulatory or erroneous compound.

中文翻译：

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神秘的5-羟甲基尿嘧啶：氧化修饰的碱基，表观遗传标记或两者兼而有之？

这篇综述的目的是描述导致5-羟甲基尿嘧啶生成的反应，以及从DNA中去除5-羟基甲基尿嘧啶所涉及的修复过程，以及其在各种细胞和尿液中的水平。5-羟甲基尿嘧啶可在以下两个过程中形成：胸腺嘧啶的氧化/羟基化，从而形成与腺嘌呤配对的5-羟甲基尿嘧啶（由活性氧产生），以及活性氧与5-甲基胞嘧啶反应形成5-羟甲基胞嘧啶，然后将其脱氨基为与鸟嘌呤错配的5-羟甲基尿嘧啶。然而，其他可能是酶的机制可能与鸟嘌呤错配的5-羟甲基尿嘧啶的形成有关。实际上，这种错配也可能是由于最近描述的“第六个” 5-羟甲基胞嘧啶脱氨基而形成的。DNA碱基。结果表明，在小鼠胚胎细胞分化过程中，胸腺嘧啶的TET酶也可以生成与腺嘌呤配对的5-羟甲基尿嘧啶。因此，5-羟甲基尿嘧啶可能是表观遗传标记。5-羟甲基尿嘧啶在各种体细胞组织中的水平相对稳定，与淋巴细胞中观察到的水平相似，在人结肠，大肠癌以及各种大鼠和猪组织中约为0.5 / 10（6）dN。实验证据表明，SMUG1和TDG是涉及从DNA去除5-羟甲基尿嘧啶的主要酶。在rRNA中还检测到了5-羟甲基尿嘧啶形式的5-羟甲基尿嘧啶，它与SMUG1一起可能在rRNA质量控制中起作用。总而言之，毫无疑问，5-羟甲基尿嘧啶是酶和反应性氧引起的反应的产物。这种修饰可能可以作为表观遗传标记，提供基因组内编码的附加信息层。然而，由于氧化应激而产生的5-羟甲基尿嘧啶池也可能干扰生理表观遗传过程，因此可以定义为病变。总之，这表明5-羟甲基尿嘧啶可能是调节性化合物或错误化合物。