A polar filter in DNA polymerases prevents ribonucleotide incorporation.
作者： Mary K Johnson , Jithesh Kottur , Deepak T Nair
DOI: 10.2210/PDB6JUS/PDB
关键词:
摘要: The presence of ribonucleotides in DNA can lead to genomic instability and cellular lethality. To prevent adventitious rNTP incorporation, the majority polymerases (dPols) possess a steric filter. dPol named MsDpo4 (Mycobacterium smegmatis) naturally lacks this filter hence is capable addition. introduction did not result complete abrogation ability enzyme incorporate ribonucleotides. In comparison, polymerase IV (PolIV) from Escherichia coli exhibited stringent selection for deoxyribonucleotides. A comparison PolIV led discovery an additional polar responsible sugar selectivity. Thr43 represents residue forms interactions with incoming nucleotide draw it closer surface. As result, 2'-OH rNTPs will clash surface, therefore cannot be accommodated active site conformation compatible productive catalysis. substitution equivalent MsDpo4-Cys47, Thr drastic reduction mycobacterial rNTPs. Overall, our studies evince that serves ribonucleotide incorporation by dPols.
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oup.com参考文章(89)
Robert E. Johnson, Roland Klassen, Louise Prakash, Satya Prakash, A Major Role of DNA Polymerase δ in Replication of Both the Leading and Lagging DNA Strands Molecular Cell. ,vol. 59, pp. 163- 175 ,(2015) , 10.1016/J.MOLCEL.2015.05.038
Jithesh Kottur, Amit Sharma, Kiran R. Gore, Naveen Narayanan, Biswajit Samanta, Pushpangadan I. Pradeepkumar, Deepak T. Nair, Unique structural features in DNA polymerase IV enable efficient bypass of the N2 adduct induced by the nitrofurazone antibiotic Structure. ,vol. 23, pp. 56- 67 ,(2015) , 10.1016/J.STR.2014.10.019
Danielle L. Watt, Erik Johansson, Peter M. Burgers, Thomas A. Kunkel, Replication of ribonucleotide-containing DNA templates by yeast replicative polymerases. DNA Repair. ,vol. 10, pp. 897- 902 ,(2011) , 10.1016/J.DNAREP.2011.05.009
N. Y. Yao, J. W. Schroeder, O. Yurieva, L. A. Simmons, M. E. O'Donnell, Cost of rNTP/dNTP pool imbalance at the replication fork. Proceedings of the National Academy of Sciences of the United States of America. ,vol. 110, pp. 12942- 12947 ,(2013) , 10.1073/PNAS.1309506110
Philip Nevin, John R. Engen, Penny J. Beuning, Steric gate residues of Y-family DNA polymerases DinB and pol kappa are crucial for dNTP-induced conformational change. DNA Repair. ,vol. 29, pp. 65- 73 ,(2015) , 10.1016/J.DNAREP.2015.01.012
Ana Bonnin, José M Lázaro, Luis Blanco, Margarita Salas, A single tyrosine prevents insertion of ribonucleotides in the eukaryotic-type φ29 DNA polymerase Journal of Molecular Biology. ,vol. 290, pp. 241- 251 ,(1999) , 10.1006/JMBI.1999.2900
Karl E Zahn, April M Averill, Pierre Aller, Richard D Wood, Sylvie Doublié, Human DNA polymerase θ grasps the primer terminus to mediate DNA repair Nature Structural & Molecular Biology. ,vol. 22, pp. 304- 311 ,(2015) , 10.1038/NSMB.2993
John P. McDonald, Alexandra Vaisman, Wojciech Kuban, Myron F. Goodman, Roger Woodgate, Mechanisms Employed by Escherichia coli to Prevent Ribonucleotide Incorporation into Genomic DNA by Pol V PLoS Genetics. ,vol. 8, pp. e1003030- ,(2012) , 10.1371/JOURNAL.PGEN.1003030
Shuangluo Xia, Jimin Wang, William H. Konigsberg, DNA mismatch synthesis complexes provide insights into base selectivity of a B family DNA polymerase. Journal of the American Chemical Society. ,vol. 135, pp. 193- 202 ,(2013) , 10.1021/JA3079048
Jessica A. Brown, Kevin A. Fiala, Jason D. Fowler, Shanen M. Sherrer, Sean A. Newmister, Wade W. Duym, Zucai Suo, A novel mechanism of sugar selection utilized by a human X-family DNA polymerase. Journal of Molecular Biology. ,vol. 395, pp. 282- 290 ,(2010) , 10.1016/J.JMB.2009.11.003