TY - JOUR
T1 - Induction of a mutant phenotype in human repair proficient cells after overexpression of a mutated human DNA repair gene
AU - Belt, Peter B.G.m.
AU - Van Oosterwijk, Michiel F.
AU - Odijk, Hanny
AU - Hoeijmakers, Jan H.J.
AU - Backendorf, Claude
N1 - Funding Information:
The authors like to thank Dr. M. van Duin for providing several ERCC-1 constructs, Dr. N.G.J. Jaspers for helpful discussions and contribution in the Western blot analysis, Dr. P. van de Putte and Dr. D. Bootsma for stimulating interest and Henriette Grote Gansey for typing the manuscript. This work was financially supported by the Netherlands Organization of Advancement of Pure Research (contract no. 900-501-091), the Dutch Cancer Society (project IKR90-20) and the J.A. Cohen Institute for Radiopathology and Radiation Protection (IRS) project no. 4.2.8.
PY - 1991/10/25
Y1 - 1991/10/25
N2 - Antisense and mutated cDNA of the human excision repair gene ERCC-1 were overexpressed in repair proficient HeLa cells by means of an Epstein-Barr-virus derived cDNA expression vector. Whereas antisense RNA did not influence the survival of the transfected cells, a mutated cDNA generating an ERCC-1 protein with two extra amino acids in a conserved region of its C-terminal part resulted in a significant sensitization of the HeLa transfectants to mitomycin C-induced damage. These results suggest that overexpression of the mutated ERCC-1 protein interferes with proper functioning of the excision rep ir pathway in repair proficient cells and is compatible with a model in which the mutated ERCC-1 protein competes with the wildtype polypeptide for a specific step in the repair process or for occupation of a site in a repair complex. Apparently, this effect is more pronounced for mitomycin C induced crosslink repair than for UVinduced DNA damage.
AB - Antisense and mutated cDNA of the human excision repair gene ERCC-1 were overexpressed in repair proficient HeLa cells by means of an Epstein-Barr-virus derived cDNA expression vector. Whereas antisense RNA did not influence the survival of the transfected cells, a mutated cDNA generating an ERCC-1 protein with two extra amino acids in a conserved region of its C-terminal part resulted in a significant sensitization of the HeLa transfectants to mitomycin C-induced damage. These results suggest that overexpression of the mutated ERCC-1 protein interferes with proper functioning of the excision rep ir pathway in repair proficient cells and is compatible with a model in which the mutated ERCC-1 protein competes with the wildtype polypeptide for a specific step in the repair process or for occupation of a site in a repair complex. Apparently, this effect is more pronounced for mitomycin C induced crosslink repair than for UVinduced DNA damage.
UR - https://www.scopus.com/pages/publications/0026075929
U2 - 10.1093/nar/19.20.5633
DO - 10.1093/nar/19.20.5633
M3 - Article
C2 - 1945841
AN - SCOPUS:0026075929
SN - 0305-1048
VL - 19
SP - 5633
EP - 5637
JO - Nucleic acids research
JF - Nucleic acids research
IS - 20
ER -