A single (6-4) photoproduct inhibits plasmid DNA replication in xeroderma pigmentosum variant cell extracts.
Environ Mol Mutagen
; 38(1): 19-29, 2001.
Article
en En
| MEDLINE
| ID: mdl-11473384
ABSTRACT
The human skin cancer-prone disease xeroderma pigmentosum variant (XPV) results from a mutation in the human RAD30 gene, which encodes the lesion bypass DNA polymerase eta. XPV cells are characterized by delayed completion of DNA replication and increased mutagenesis following UV-irradiation. Using extracts of an XPV lymphoblast cell line (GM2449C) that has a truncating mutation in the RAD30 gene, we investigated the effect of a (6-4) photoproduct and a cyclobutane pyrimidine dimer (CPD), at a unique -TT- site on either the leading or lagging strand, on plasmid DNA replication. Compared to normal cell extracts, XPV cell extracts have a reduced capacity to carry out complete replication of DNA containing either a (6-4) photoproduct or a CPD on the leading strand, whereas there is little difference between the two cell extracts in replication of DNA containing a lesion on the lagging strand. Inhibition of replication in the presence of a (6-4) photoproduct is attributed to arrest of nascent DNA strand synthesis at the lesion site; in XPV cell extracts, the proportion of arrested products is increased compared to that of normal cell extracts. These results are consistent with a requirement for functional DNA polymerase eta in the replication of a double-stranded plasmid containing either a (6-4) photoproduct or a CPD, on the leading but not the lagging strand.
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Base de datos:
MEDLINE
Asunto principal:
Plásmidos
/
Dímeros de Pirimidina
/
Xerodermia Pigmentosa
/
Replicación del ADN
Idioma:
En
Revista:
Environ Mol Mutagen
Asunto de la revista:
BIOLOGIA MOLECULAR
/
SAUDE AMBIENTAL
Año:
2001
Tipo del documento:
Article
País de afiliación:
Estados Unidos