Life without dUTPase.
Life without dUTPase.
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DOI：
10.3389/fmicb.2016.01768
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发表时间：
2016
影响因子：
5.2
通讯作者：
Vértessy BG
中科院分区：
文献类型：
--
作者：
Kerepesi C;Szabó JE;Papp-Kádár V;Dobay O;Szabó D;Grolmusz V;Vértessy BG
细胞核苷酸库的微调调节对于脱氧核糖核酸（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。两种酶活性主要涉及保持DNA尿嘧啶游离：dUTP焦磷酸酶（dUTP焦磷酸酶）活性，其防止胸腺嘧啶取代掺入;尿嘧啶-DNA糖基化酶活性，其从DNA切除尿嘧啶并启动尿嘧啶切除修复。脱氧尿苷和最有效的尿嘧啶-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。我们已经进行了生物信息学搜索，在这些基因组中使用已经很好地描述的dUTR和UNG基因序列。对于dUTPases，我们已经包括三聚体全β和二聚体全α家族以及双功能dCTP（脱氧胞苷三磷酸）脱氨酶-dUTPases序列。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所有先前描述的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。我们讨论了潜在的生存策略缺乏dUTPases，如同时缺乏或抑制UNG和拥有外源性或替代代谢酶参与尿嘧啶-DNA代谢。还讨论了以前与dUTP活性无关的基因仍可能编码能够水解dUTP的酶的可能性。我们的数据表明，几种单细胞微生物可以有效地科普缺乏所有先前描述的dUTR基因的dut-基因型，并可能导致其基因组DNA中不寻常的尿嘧啶富集。
Fine-tuned regulation of the cellular nucleotide pools is indispensable for faithful replication of Deoxyribonucleic Acid (DNA). The genetic information is also safeguarded by DNA damage recognition and repair processes. Uracil is one of the most frequently occurring erroneous bases in DNA; it can arise from cytosine deamination or thymine-replacing incorporation. Two enzyme activities are primarily involved in keeping DNA uracil-free: dUTPase (dUTP pyrophosphatase) activity that prevent thymine-replacing incorporation and uracil-DNA glycosylase activity 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. We have performed bioinformatic searches in these genomes using the already well described dUTPase and UNG gene sequences. For dUTPases, we have included the trimeric all-beta and the dimeric all-alpha families and also, the bifunctional dCTP (deoxycytidine triphosphate) deaminase-dUTPase sequences. Surprisingly, we have found that in contrast to the generally held opinion, a wide number of bacterial and Archaeal species lack all of the previously described 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 discuss potential survival strategies in lack of dUTPases, such as simultaneous lack or inhibition of UNG and possession of exogenous or alternate metabolic enzymes involved in uracil-DNA metabolism. The potential that genes previously not associated with dUTPase activity may still encode enzymes capable of hydrolyzing dUTP is also discussed. Our data indicate that several unicellular microorganisms may efficiently cope with a dut– genotype lacking all of the previously described dUTPase genes, and potentially leading to an unusual uracil-enrichment in their genomic DNA.
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影响因子：
64.5
作者：
Boshoff, HIM;Reed, MB;Mizrahi, V
通讯作者：
Mizrahi, V
影响因子：
4.8
作者：
Björnberg, O;Neuhard, J;Nyman, PO
通讯作者：
Nyman, PO
DOI：
10.1016/j.biocel.2012.06.014
发表时间：
2012-09-01
影响因子：
4
作者：
Castillo-Acosta, Victor M.;Aguilar-Pereyra, Fernando;Gonzalez-Pacanowska, Dolores
通讯作者：
Gonzalez-Pacanowska, Dolores
影响因子：
14.9
作者：
Cole AR;Ofer S;Ryzhenkova K;Baltulionis G;Hornyak P;Savva R
通讯作者：
Savva R
影响因子：
3.2
作者：
Kana, BD;Mizrahi, V
通讯作者：
Mizrahi, V