The repair of 4-nitroquinoline-1-oxide induced DNA adducts in hypersensitive Chinese hamster mutants: lack of repair of UV induced (6-4) photoproduct correlates with reduced repair of adducts at the N2 of guanosine.
UV sensitive Chinese hamster mutants belonging to ERCC groups 1, 2 and 6 together with one cross-link- and one X-ray-sensitive mutant have been examined for sensitivity to 4-nitroquinoline-1-oxide (4NQO) and the ability to repair 4NQO adducts at the N2 and C8 of guanosine. Despite the fact that all of the mutants examined were hyper-sensitive to 4NQO there was little difference between the mutants V-H1, V-H4, V-C4 and UV61 and the parental cell lines as regards the ability to remove these lesions from bulk DNA. The UV5 and UV20 mutants were both defective in the ability to remove N2 guanosine adducts yet repaired the C8 guanine adduct as normal. The fact that the mutants V-H1, V-H4, V-C4 and UV61 are 4NQO sensitive but repair the above adducts suggests that either some other lesion(s) is responsible for increased toxicity in these mutants, or that some regions of the genome may not be repaired as effectively as bulk DNA in these mutants, or that the quality of the repair is less than in the parental cells. Clearly the inability to remove UV induced pyrimidine dimers and the (6-4) photoproduct associated with the UV5 and UV20 mutants correlates with the inability to repair 4NQO-N2 guanosine adducts. However, mutants capable of (6-4) photoproduct repair but not dimer repair (VH-1 and UV61) can repair this lesion. Hence it is possible that the same domains in these repair proteins are required for the recognition of (6-4) photoproduct repair and 4NQO-N2 guanosine adducts.(ABSTRACT TRUNCATED AT 250 WORDS)
Yang
A L
AL
School of Biological Sciences, University College of Swansea, UK.
Zdzienicka
M Z
MZ
Simons
J W
JW
Waters
R
R
D015112:4-Nitroquinoline-1-oxide / Q000494:pharmacology*; D000818:Animals; D016923:Cell Death; D002460:Cell Line; D006224:Cricetinae; D004247:DNA / Q000187:drug effects* / Q000528:radiation effects; D004260:DNA Repair; D006151:Guanosine / Q000378:metabolism; D009154:Mutation; D014466:Ultraviolet Rays
D006151:Guanosine; D015112:4-Nitroquinoline-1-oxide; D004247:DNA