Structural basis of DNA synthesis opposite 8-oxoguanine by human PrimPol primase-polymerase.
Nat Commun
; 12(1): 4020, 2021 06 29.
Article
em En
| MEDLINE
| ID: mdl-34188055
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)â¢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.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Dano ao DNA
/
DNA Primase
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Pareamento de Bases
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DNA Polimerase Dirigida por DNA
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Replicação do DNA
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Enzimas Multifuncionais
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Guanina
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article