2DPI

Ternary complex of hPoli with DNA and dCTP

Summary for 2DPI

• Entry DOI: 10.2210/pdb2dpi/pdb
• Related: 1T3N 2ALZ 2DPJ
• Descriptor: 5'-D(*AP*GP*GP*AP*CP*CP*(DOC))-3', 5'-D(*TP*(EDA)P*GP*GP*GP*TP*CP*CP*T)-3', DNA polymerase iota, ... (6 entities in total)
• Functional Keywords: dna dependent dna polymerase, ethenoda adduct, lesion bypass, transferase-dna complex, transferase/dna
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus: Q9UNA4
• Total number of polymer chains: 3
• Total formula weight: 52405.35

Authors

Nair, D.T.,Johnson, R.E.,Prakash, L.,Prakash, S.,Aggarwal, A.K. (deposition date: 2006-05-12, release date: 2006-07-04, Last modification date: 2023-10-25)

Primary citation

Nair, D.T.,Johnson, R.E.,Prakash, L.,Prakash, S.,Aggarwal, A.K.
Hoogsteen base pair formation promotes synthesis opposite the 1,N(6)-ethenodeoxyadenosine lesion by human DNA polymerase iota.
Nat.Struct.Mol.Biol., 13:619-625, 2006

PubMed 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.

PubMed: 16819516
DOI: 10.1038/nsmb1118

Experimental method

X-RAY DIFFRACTION (2.3 Å)