7JKL

Human PrimPol misinserting dATP opposite the 8-oxoguanine lesion (3'-end base of the primer strand is 2',3'-dideoxy-terminated).

7JKL の概要

• エントリーDOI: 10.2210/pdb7jkl/pdb
• 関連するPDBエントリー: 7JK1
• 分子名称: DNA-directed primase/polymerase protein, DNA (5'-D(P*AP*(8OG)P*CP*GP*CP*TP*AP*CP*CP*AP*CP*AP*CP*CP*CP*C)-3'), DNA (5'-D(*GP*GP*GP*TP*GP*TP*GP*GP*TP*AP*GP*CP*(DDG))-3'), ... (7 entities in total)
• 機能のキーワード: translesion, dna synthesis, dna replication, dna damage, transferase, transferase-dna complex, transferase/dna
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 101695.66

構造登録者

Rechkoblit, O.,Aggarwal, A.K. (登録日: 2020-07-28, 公開日: 2021-06-30, 最終更新日: 2023-10-18)

主引用文献

Rechkoblit, O.,Johnson, R.E.,Gupta, Y.K.,Prakash, L.,Prakash, S.,Aggarwal, A.K.
Structural basis of DNA synthesis opposite 8-oxoguanine by human PrimPol primase-polymerase.
Nat Commun, 12:4020-4020, 2021

PubMed Abstract: PrimPol is a human DNA polymerase-primase that localizes to mitochondria and nucleus and bypasses the major oxidative lesion 7,8-dihydro-8-oxoguanine (oxoG) via translesion synthesis, in mostly error-free manner. We present structures of PrimPol insertion complexes with a DNA template-primer and correct dCTP or erroneous dATP opposite the lesion, as well as extension complexes with C or A as a 3'-terminal primer base. We show that during the insertion of C and extension from it, the active site is unperturbed, reflecting the readiness of PrimPol to accommodate oxoG(anti). The misinsertion of A opposite oxoG(syn) also does not alter the active site, and is likely less favorable due to lower thermodynamic stability of the oxoG(syn)•A base-pair. During the extension step, oxoG(syn) induces an opening of its base-pair with A or misalignment of the 3'-A primer terminus. Together, the structures show how PrimPol accurately synthesizes DNA opposite oxidatively damaged DNA in human cells.

PubMed: 34188055
DOI: 10.1038/s41467-021-24317-z

実験手法

X-RAY DIFFRACTION (2.384 Å)