2DPI: Ternary Complex Of Hpoli With Dna And Dctp

Citation:
Abstract
The 1,N6-ethenodeoxyadenosine (epsilon dA) lesion is promutagenic and has been implicated in carcinogenesis. We show here that human Pol iota, a Y-family DNA polymerase, can promote replication through this lesion by proficiently incorporating a nucleotide opposite it. The structural basis of this action is rotation of the epsilon dA adduct to the syn conformation in the Pol iota active site and presentation of its 'Hoogsteen edge' for hydrogen-bonding with incoming dTTP or dCTP. We also show that Pol zeta carries out the subsequent extension reaction and that efficiency of extension from epsilon dA x T is notably higher than from epsilon dA x C. Together, our studies reveal for the first time how the exocyclic epsilon dA adduct is accommodated in a DNA polymerase active site, and they show that the combined action of Pol iota and Pol zeta provides for efficient and error-free synthesis through this potentially carcinogenic DNA lesion.
PDB ID: 2DPIDownload
MMDB ID: 87026
PDB Deposition Date: 2006/5/12
Updated in MMDB: 2010/12
Experimental Method:
x-ray diffraction
Resolution: 2.3  Å
Source Organism:
synthetic construct
Similar Structures:
Biological Unit for 2DPI: hexameric; determined by author
Molecular Components in 2DPI
Label Count Molecule
Proteins (2 molecules)
2
DNA Polymerase Iota(Gene symbol: POLI)
Molecule annotation
Nucleotides(2 molecules)
2
5'-d(*ap*gp*gp*ap*cp*cp*(doc))-3'
Molecule annotation
2
5'-d(*tp*(eda)p*gp*gp*gp*tp*cp*cp*t)-3'
Molecule annotation
Chemicals (6 molecules)
1
4
2
2
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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