| Structural highlights
3g6x is a 3 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , |
| NonStd Res: | , |
| Related: | 2fll, 3g6v, 3g6y |
| Gene: | POLI, RAD30B (HUMAN) |
| Activity: | DNA-directed DNA polymerase, with EC number 2.7.7.7 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[POLI_HUMAN] Error-prone DNA polymerase specifically involved in DNA repair. Plays an important role in translesion synthesis, where the normal high-fidelity DNA polymerases cannot proceed and DNA synthesis stalls. Favors Hoogsteen base-pairing in the active site. Inserts the correct base with high-fidelity opposite an adenosine template. Exhibits low fidelity and efficiency opposite a thymidine template, where it will preferentially insert guanosine. May play a role in hypermutation of immunogobulin genes. Forms a Schiff base with 5'-deoxyribose phosphate at abasic sites, but may not have lyase activity.[1] [2] [3] [4] [5] [6] [7]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Abasic sites are among the most abundant DNA lesions formed in human cells, and they present a strong block to replication. DNA polymerase iota (Poliota) is one of the few DNA Pols that does not follow the A-rule opposite an abasic site. We present here three structures of human Poliota in complex with DNAs containing an abasic lesion and dGTP, dTTP, or dATP as the incoming nucleotide. The structures reveal a mechanism of translesion synthesis across an abasic lesion that differs from that in other Pols. Both the abasic lesion and the incoming dNTPs are intrahelical and are closely apposed across a constricted active site cleft. The dNTPs partake in distinct networks of hydrogen bonds in the "void" opposite the lesion. These different patterns of hydrogen bonds, as well as stacking interactions, may underlie Poliota's small preference for insertion of dGTP over other nucleotides opposite this common lesion.
DNA synthesis across an abasic lesion by human DNA polymerase iota.,Nair DT, Johnson RE, Prakash L, Prakash S, Aggarwal AK Structure. 2009 Apr 15;17(4):530-7. PMID:19368886[8]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Tissier A, Frank EG, McDonald JP, Iwai S, Hanaoka F, Woodgate R. Misinsertion and bypass of thymine-thymine dimers by human DNA polymerase iota. EMBO J. 2000 Oct 2;19(19):5259-66. PMID:11013228 doi:http://dx.doi.org/10.1093/emboj/19.19.5259
- ↑ Bebenek K, Tissier A, Frank EG, McDonald JP, Prasad R, Wilson SH, Woodgate R, Kunkel TA. 5'-Deoxyribose phosphate lyase activity of human DNA polymerase iota in vitro. Science. 2001 Mar 16;291(5511):2156-9. PMID:11251121 doi:http://dx.doi.org/10.1126/science.1058386
- ↑ Frank EG, Tissier A, McDonald JP, Rapic-Otrin V, Zeng X, Gearhart PJ, Woodgate R. Altered nucleotide misinsertion fidelity associated with poliota-dependent replication at the end of a DNA template. EMBO J. 2001 Jun 1;20(11):2914-22. PMID:11387224 doi:http://dx.doi.org/10.1093/emboj/20.11.2914
- ↑ Faili A, Aoufouchi S, Flatter E, Gueranger Q, Reynaud CA, Weill JC. Induction of somatic hypermutation in immunoglobulin genes is dependent on DNA polymerase iota. Nature. 2002 Oct 31;419(6910):944-7. PMID:12410315 doi:http://dx.doi.org/10.1038/nature01117
- ↑ Haracska L, Prakash L, Prakash S. A mechanism for the exclusion of low-fidelity human Y-family DNA polymerases from base excision repair. Genes Dev. 2003 Nov 15;17(22):2777-85. PMID:14630940 doi:10.1101/gad.1146103
- ↑ Washington MT, Minko IG, Johnson RE, Wolfle WT, Harris TM, Lloyd RS, Prakash S, Prakash L. Efficient and error-free replication past a minor-groove DNA adduct by the sequential action of human DNA polymerases iota and kappa. Mol Cell Biol. 2004 Jul;24(13):5687-93. PMID:15199127 doi:http://dx.doi.org/10.1128/MCB.24.13.5687-5693.2004
- ↑ Nair DT, Johnson RE, Prakash S, Prakash L, Aggarwal AK. Replication by human DNA polymerase-iota occurs by Hoogsteen base-pairing. Nature. 2004 Jul 15;430(6997):377-80. PMID:15254543 doi:10.1038/nature02692
- ↑ Nair DT, Johnson RE, Prakash L, Prakash S, Aggarwal AK. DNA synthesis across an abasic lesion by human DNA polymerase iota. Structure. 2009 Apr 15;17(4):530-7. PMID:19368886 doi:10.1016/j.str.2009.02.015
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