Abnormal kinetics of induction of UV-stimulated recombination in human DNA repair disorders.
Recombination can result in genetic instability, and thus constitutes an important factor in the carcinogenic conversion of mammalian cells. Here we describe the occurrence of UV-stimulated recombination called enhanced recombination (EREC), measured with the use of Herpes Simplex Viruses type 1 mutants. In normal diploid human cells, EREC is induced by UV-C, mitomycin C and ENU, but not by X-ray or MMS. The kinetics of induction of EREC is similar to that of other SOS-like responses such as enhanced reactivation (ER) and enhanced mutagenesis (EM). In contrast to the latter responses, EREC is induced to higher levels and persists for longer periods in DNA repair deficient fibroblasts derived from xeroderma pigmentosum (XP), Cockayne syndrome (CS) and Trichothiodystrophy (TTD) patients. This observation indicates that EREC is a distinct SOS-like response. Apparently, the presence of unrepaired DNA lesions in the host genome is a strongly inducing signal for EREC. On the other hand, in cells derived from patients suffering from Bloom, Werner or Rothmund-Thomson syndrome (RTS) the EREC response is absent. These data indicate that determining EREC is a useful assay to investigate diploid human fibroblasts for abnormalities in UV-stimulated recombination.
Department of Toxicogenetics, Leiden University Medical Center, Wassenaarseweg 72, 2333 Al Leiden, The Netherlands. p.j.abrahams@lumc.nl
Peter J
PJ
Abrahams
Ada
A
Houweling
Ron
R
Schouten
Alex J
AJ
van der Eb
Carrol
C
Terleth
D000818:Animals; D002478:Cells, Cultured; D003057:Cockayne Syndrome / Q000235:genetics*; D006224:Cricetinae; D003412:Cricetulus; D004249:DNA Damage; D004260:DNA Repair; D004307:Dose-Response Relationship, Radiation; D005347:Fibroblasts / Q000378:metabolism / Q000528:radiation effects; D006201:Hair Diseases / Q000235:genetics*; D018259:Herpesvirus 1, Human / Q000235:genetics; D006801:Humans; D007700:Kinetics; D009154:Mutation; D011995:Recombination, Genetic; D012867:Skin / Q000166:cytology; D013997:Time Factors; D014466:Ultraviolet Rays; D014983:Xeroderma Pigmentosum / Q000235:genetics*