Creative template-dependent synthesis by human polymerase mu.
Proc Natl Acad Sci U S A
; 112(33): E4530-6, 2015 Aug 18.
Article
en En
| MEDLINE
| ID: mdl-26240373
Among the many proteins used to repair DNA double-strand breaks by nonhomologous end joining (NHEJ) are two related family X DNA polymerases, Pol λ and Pol µ. Which of these two polymerases is preferentially used for filling DNA gaps during NHEJ partly depends on sequence complementarity at the break, with Pol λ and Pol µ repairing complementary and noncomplementary ends, respectively. To better understand these substrate preferences, we present crystal structures of Pol µ on a 2-nt gapped DNA substrate, representing three steps of the catalytic cycle. In striking contrast to Pol λ, Pol µ "skips" the first available template nucleotide, instead using the template base at the 5' end of the gap to direct nucleotide binding and incorporation. This remarkable divergence from canonical 3'-end gap filling is consistent with data on end-joining substrate specificity in cells, and provides insights into polymerase substrate choices during NHEJ.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
ADN
/
ADN Polimerasa Dirigida por ADN
/
Reparación del ADN
Límite:
Humans
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Año:
2015
Tipo del documento:
Article
Pais de publicación:
Estados Unidos