Human chromosome 5 complements the DNA double-strand break-repair deficiency and gamma-ray sensitivity of the XR-1 hamster variant.
XR-1 is a Chinese hamster ovary (CHO) cell mutant which is unusually sensitive to killing by gamma rays in the G1 portion of the cell cycle but has nearly normal resistance to gamma-ray damage in late S phase. The cell-cycle sensitivity correlates with the mutant's inability to repair DNA double-strand breaks (DSBs) produced by ionizing radiation and restriction enzymes. We have previously shown in somatic cell hybrids of XR-1 cells and human fibroblasts that the XR-1 mutation is a recessive mutation. In this study, using somatic cell hybrids formed between XR-1 and human fibroblasts, we map the human complementing gene to chromosome 5 by chromosome-segregation analysis. This gene biochemically restores the hamster defect to wild-type levels of gamma-ray and bleomycin resistance as well as restoring its proficiency to repair DNA DSBs, suggesting that a single gene is responsible for the XR-1 phenotype. We have tentatively assigned the name XRCC4 (X-ray-complementing Chinese hamster gene 4) to this human gene until its biochemical function in repair is discovered.
Wistar Institute of Anatomy and Biology, Philadelphia, PA.
A J
AJ
Giaccia
N
N
Denko
R
R
MacLaren
D
D
Mirman
C
C
Waldren
I
I
Hart
T D
TD
Stamato
D000818:Animals; D001761:Bleomycin / Q000494:pharmacology; D002453:Cell Cycle; D002460:Cell Line; D002874:Chromosome Mapping; D002895:Chromosomes, Human, Pair 5; D006224:Cricetinae; D004247:DNA / Q000528:radiation effects; D004249:DNA Damage; D004260:DNA Repair; D004351:Drug Resistance; D005347:Fibroblasts; D005720:Gamma Rays; D005816:Genetic Complementation Test; D006801:Humans; D006822:Hybrid Cells; D007621:Karyotyping; D009154:Mutation; D010641:Phenotype
D001761:Bleomycin; D004247:DNA