2GWS

Crystal Structure of human DNA Polymerase lambda with a G/G mismatch in the primer terminus

2GWS の概要

• エントリーDOI: 10.2210/pdb2gws/pdb
• 分子名称: 5'-D(*CP*GP*GP*CP*AP*GP*CP*GP*CP*AP*C)-3', 5'-D(*GP*TP*GP*CP*GP*G)-3', 5'-D(P*GP*CP*CP*G)-3', ... (10 entities in total)
• 機能のキーワード: dna polymerase lambda, family x, mismatch extension, mutagenesis, nhej, transferase-dna complex, transferase/dna
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus : Q9UGP5
• タンパク質・核酸の鎖数: 16
• 化学式量合計: 176302.77

構造登録者

Garcia-Diaz, M.,Picher, A.J.,Bebenek, K.,Pedersen, L.C.,Kunkel, T.A.,Blanco, L. (登録日: 2006-05-05, 公開日: 2006-09-05, 最終更新日: 2024-11-13)

主引用文献

Picher, A.J.,Garcia-Diaz, M.,Bebenek, K.,Pedersen, L.C.,Kunkel, T.A.,Blanco, L.
Promiscuous mismatch extension by human DNA polymerase lambda.
Nucleic Acids Res., 34:3259-3266, 2006

PubMed Abstract: DNA polymerase lambda (Pol lambda) is one of several DNA polymerases suggested to participate in base excision repair (BER), in repair of broken DNA ends and in translesion synthesis. It has been proposed that the nature of the DNA intermediates partly determines which polymerase is used for a particular repair reaction. To test this hypothesis, here we examine the ability of human Pol lambda to extend mismatched primer-termini, either on 'open' template-primer substrates, or on its preferred substrate, a 1 nt gapped-DNA molecule having a 5'-phosphate. Interestingly, Pol lambda extended mismatches with an average efficiency of approximately 10(-2) relative to matched base pairs. The match and mismatch extension catalytic efficiencies obtained on gapped molecules were approximately 260-fold higher than on template-primer molecules. A crystal structure of Pol lambda in complex with a single-nucleotide gap containing a dG.dGMP mismatch at the primer-terminus (2.40 A) suggests that, at least for certain mispairs, Pol lambda is unable to differentiate between matched and mismatched termini during the DNA binding step, thus accounting for the relatively high efficiency of mismatch extension. This property of Pol lambda suggests a potential role as a 'mismatch extender' during non-homologous end joining (NHEJ), and possibly during translesion synthesis.

PubMed: 16807316
DOI: 10.1093/nar/gkl377

実験手法

X-RAY DIFFRACTION (2.4 Å)