没有dUTPase的生活
Life without dUTPase
摘要：
细胞核苷酸库的微调调节对于DNA的忠实复制是必不可少的。遗传信息也受到DNA损伤识别和修复过程的保护。尿嘧啶是DNA中最常见的错误碱基之一，它可以由胞嘧啶脱氨基或胸腺嘧啶取代掺入引起。两个酶家族主要参与保持DNA尿嘧啶游离：防止胸腺嘧啶取代掺入的dUTPases和从DNA切除尿嘧啶并启动尿嘧啶切除修复的尿嘧啶-DNA糖基化酶。dUTR和最有效的尿嘧啶-DNA糖基化酶UNG被认为在自由生活的生物体中普遍存在。在目前的工作中，我们已经系统地调查了基因型的完全测序的细菌和细菌基因组。令人惊讶的是，我们发现，与普遍持有的观点相反，大量的细菌和真菌物种缺乏dUTR基因。dut-基因型存在于不同的细菌门中，表明在进化过程中这种（或这些）基因的丢失已经发生多次。我们已经确定了几种缺乏dUTP酶的生存策略：i）同时缺乏或抑制UNG，ii）获得较少的dUTP特异性消毒核苷酸焦磷酸酶，和iii）从噬菌体供应dUTP酶。我们的数据表明，几种单细胞微生物可以有效地应对dut-基因型，可能导致其基因组DNA中不寻常的尿嘧啶富集。
英文摘要：
Fine-tuned regulation of the cellular nucleotide pools is indispensable for faithful replication of DNA. The genetic information is also safeguarded by DNA damage recognition and repair processes. Uracil is one of the most frequently occurring erroneous base in DNA; it can arise from cytosine deamination or thymine-replacing incorporation. Two enzyme families are primarily involved in keeping DNA uracil-free: dUTPases that prevent thymine-replacing incorporation and uracil-DNA glycosylases that excise uracil from DNA and initiate uracil-excision repair. Both dUTPase and the most efficient uracil-DNA glycosylase UNG is thought to be ubiquitous in free-living organisms. In the present work, we have systematically investigated the genotype of deposited fully sequenced bacterial and Archaeal genomes. Surprisingly, we have found that in contrast to the generally held opinion, a wide number of bacterial and Archaeal species lack the dUTPase gene(s). The dut- genotype is present in diverse bacterial phyla indicating that loss of this (or these) gene(s) has occurred multiple times during evolution. We have identified several survival strategies in lack of dUTPases: i) simultaneous lack or inhibition of UNG, ii) acquisition of a less dUTP-specific sanitizing nucleotide pyrophosphatase, and iii) supply of dUTPase from bacteriophages. Our data indicate that several unicellular microorganisms may efficiently cope with a dut- genotype potentially leading to an unusual uracil-enrichment in their genomic DNA.
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