REGIONAL MAPPING OF HUMAN DNA EXCISION REPAIR GENE ERCC4 TO CHROMOSOME-16P13.13-P13.2

Mitomycin C (MMC)-resistant interspecific somatic cell hybrids made be tween human cells and the MMC-sensitive, Chinese hamster ovary (CHO) e xcision repair-deficient UV41 cells generally contained human chromoso me 16, while other human chromosomes were randomly present. MMC-sensit ive and -resistant subclones were isolated from resistant clones, and resistance generally segregated concordantly with human chromosome 16 markers. UV radiation survival analysis of subclones indicated that MM C and UV resistance were correlated. Therefore, the complementing gene , Excision Repair Cross Complementing 4 (ERCC4), was assigned to human chromosome 16. Complementation of UV41 by human cells derived from pa tients with xeroderma pigmentosum groups A, C, D and F excluded ERCC4 from involvement in those disease syndromes. Resistant hybrids contain ing only portions of chromosome 16 were identified by the lack of conc ordance of multiple chromosome 16 markers. When such hybrids were used as a source of probe for fluorescent in situ hybridization onto norma l human metaphases, the only region of chromosome 16 identified as bei ng consistently present was 16p13.1-p13.3. Genetic marker analysis of informative hybrids with mapped probes refined the position of ERCC4 t o 16p13.13-p13.2 and allowed the following order of markers within the region to be established: pter- (PRM1, )-D16S213-D16S53-(D16S214,ERCC 4)-D16S3-D16S96-cen.