Computational identification of novel biochemical systems involved in oxidation, glycosylation and other complex modifications of bases in DNA.
Computational identification of novel biochemical systems involved in oxidation, glycosylation and other complex modifications of bases in DNA.
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DOI：
10.1093/nar/gkt573
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发表时间：
2013-09
影响因子：
14.9
通讯作者：
Aravind L
中科院分区：
文献类型：
--
作者：
Iyer LM;Zhang D;Burroughs AM;Aravind L
修饰DNA中碱基的双加氧酶的泰特/JBP家族的发现引发了对新的DNA碱基修饰及其生物学作用的相当大的兴趣。使用敏感的序列和结构分析，结合比较基因组学的背景信息，我们计算表征超过12种新的生化系统的DNA修饰。我们预测以前未确定的酶，如动质体J-基地产生糖基转移酶（及其同系物GREB 1），噬菌体泰特/JBP蛋白的催化特异性和它们在复杂的DNA碱基修饰的作用。我们还预测了参与超修饰碱基合成的酶，如α-谷氨酰胸腺嘧啶和α-腐胺酰胸腺嘧啶，它们几十年来一直是个谜。此外，目前的分析表明，噬菌体和某些核质大DNA病毒含有出乎意料的多样性的DNA修饰系统，除了那些使用以前表征的酶，如Dam，Dcm，泰特/JBP，嘧啶羟甲基化酶，妈妈和糖基转移酶。这些包括产生修饰的碱基的酶，例如与精氨酸和古核苷相关的脱氮鸟嘌呤，与赖氨酸相当的嘧啶，使用修饰的S-腺苷甲硫氨酸衍生物衍生的那些和使用泰特/JBP产生的羟甲基嘧啶作为生物合成起始点的那些。我们提出的证据表明，这些修饰系统中的一些也广泛分布在原核生物和某些真核生物，如担子菌，绿藻和strateconiile的，在那里他们可以作为新的表观遗传标记的调节或歧视的自我从非自我的DNA。我们的研究扩展了PUA样折叠结构域在识别修饰的核酸中的作用，并预测了ASCH和EVE结构域的版本是DNA中修饰碱基的新“读者”。这些结果为研究这些系统的生物学及其在生物技术中的应用提供了机会。
Discovery of the TET/JBP family of dioxygenases that modify bases in DNA has sparked considerable interest in novel DNA base modifications and their biological roles. Using sensitive sequence and structure analyses combined with contextual information from comparative genomics, we computationally characterize over 12 novel biochemical systems for DNA modifications. We predict previously unidentified enzymes, such as the kinetoplastid J-base generating glycosyltransferase (and its homolog GREB1), the catalytic specificity of bacteriophage TET/JBP proteins and their role in complex DNA base modifications. We also predict the enzymes involved in synthesis of hypermodified bases such as alpha-glutamylthymine and alpha-putrescinylthymine that have remained enigmatic for several decades. Moreover, the current analysis suggests that bacteriophages and certain nucleo-cytoplasmic large DNA viruses contain an unexpectedly diverse range of DNA modification systems, in addition to those using previously characterized enzymes such as Dam, Dcm, TET/JBP, pyrimidine hydroxymethylases, Mom and glycosyltransferases. These include enzymes generating modified bases such as deazaguanines related to queuine and archaeosine, pyrimidines comparable with lysidine, those derived using modified S-adenosyl methionine derivatives and those using TET/JBP-generated hydroxymethyl pyrimidines as biosynthetic starting points. We present evidence that some of these modification systems are also widely dispersed across prokaryotes and certain eukaryotes such as basidiomycetes, chlorophyte and stramenopile alga, where they could serve as novel epigenetic marks for regulation or discrimination of self from non-self DNA. Our study extends the role of the PUA-like fold domains in recognition of modified nucleic acids and predicts versions of the ASCH and EVE domains to be novel ‘readers’ of modified bases in DNA. These results open opportunities for the investigation of the biology of these systems and their use in biotechnology.
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影响因子：
2.9
作者：
Bertonati, Claudia;Punta, Marco;Fischer, Markus;Yachdav, Guy;Forouhar, Farhad;Zhou, Weihong;Kuzin, Alexander P.;Seetharaman, Jayaraman;Abashidze, Mariam;Ramelot, Theresa A.;Kennedy, Michael A.;Cort, John R.;Belachew, Adam;Hunt, John F.;Tong, Liang;Montelione, Gaetano T.;Rost, Burkhard
通讯作者：
Rost, Burkhard
影响因子：
2.9
作者：
Burroughs, A. Maxwell;Iyer, Lakshminarayan M.;Aravind, L.
通讯作者：
Aravind, L.
影响因子：
14.9
作者：
Cole C;Barber JD;Barton GJ
通讯作者：
Barton GJ
影响因子：
3.9
作者：
Aravind, L;Koonin, EV
通讯作者：
Koonin, EV
影响因子：
13.8
作者：
Dandekar, T;Snel, B;Bork, P
通讯作者：
Bork, P