Differential repair of DNA damage in the human metallothionein gene family.
We studied the repair of UV- and aflatoxin B1 (AFB1)-induced damage in the human metallothionein (hMT) gene family. After exposure to either UV or AFB1, DNA damage was initially repaired faster in the DNA fragments containing the transcribed hMT-IA, hMT-IE, and hMT-IIA genes than in the genome overall. By 6 h posttreatment, there was at least twice as much repair in these genes as in the rest of the genome. Repair of UV damage in the hMT-IB gene, which shows cell-type specific expression, and in the hMT-IIB gene, which is a nontranscribed processed pseudogene, was about the same as in the rest of the genome, whereas repair of AFB1-induced damage was deficient in these two genes. Inducing transcription of the three expressed hMT genes with CdCl2 or of only the hMT-IIA gene with dexamethasone increased the initial rate of repair in the induced genes another twofold over the rate observed when they were transcribed at a basal level. The rates of repair in the hMT-IB and hMT-IIB genes were not altered by these inducing treatments. Transcription of the hMT genes was transiently inhibited after UV irradiation. Inducing transcription of the genes did not shorten this UV-induced delay. Thus, the efficiency of repair of damage in a DNA sequence is dependent on the level of transcriptional activity associated with that sequence. However, an increased efficiency in repair of a gene itself is not necessarily coupled to recovery of its transcription after DNA damage.
Leadon
S A
SA
Division of Cell and Molecular Biology, Lawrence Berkeley Laboratory, University of California, Berkeley 94720.
Snowden
M M
MM
D016604:Aflatoxin B1; D000348:Aflatoxins / Q000494:pharmacology; D002460:Cell Line; D004249:DNA Damage; D004260:DNA Repair; D004273:DNA, Neoplasm / Q000235:genetics; D005796:Genes / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D007700:Kinetics; D008668:Metallothionein / Q000235:genetics*; D005810:Multigene Family; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D014466:Ultraviolet Rays
D000348:Aflatoxins; D004273:DNA, Neoplasm; D012334:RNA, Neoplasm; D008668:Metallothionein; D016604:Aflatoxin B1