Peer-Reviewed Journal Details
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Yao, JQ;Dixon, K;Carty, MP
2001
January
Environmental And Molecular Mutagenesis
A single (6-4) photoproduct inhibits plasmid DNA replication in xeroderma pigmentosum variant cell extracts
Published
WOS: 13 ()
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THYMINE-THYMINE DIMER ESCHERICHIA-COLI DINB SIMIAN VIRUS-40 DNA UV-INDUCED LESION ULTRAVIOLET-LIGHT POLYMERASE-ETA POSTREPLICATION REPAIR TRANSLESION SYNTHESIS PYRIMIDINE DIMERS EXCISION-REPAIR
38
19
29
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 logging 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 logging 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. (C) 2001 Wiley-Liss, Inc.
0893-6692
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