THE HUMAN DNA-POLYMERASE BETA-GENE STRUCTURE - EVIDENCE OF ALTERNATIVE SPLICING IN GENE-EXPRESSION

DNA polymerase beta (beta-pol) is a single-copy gene that is considere d to be part of the DNA repair machinery in mammalian cells. Using two human genomic libraries we have cloned the complete human beta-pol ge ne and determined the organization of the beta-pol coding sequence wit hin the gene. The human beta-pol gene spans 33 kb and contains 14 exon s that range from 50 to 233 bp. The 13 introns vary from 96 bp to 6.5 kb. Information derived from this study was used in defining the locat ion of a deletion/insertion type restriction fragment length polymorph ism (RFLP) 5' to exon I of the human beta-pol gene. This RFLP was util ized in linkage analysis of DNAs from CEPH families and the results co nfirm the previous assignment of the human beta-pol gene to chromosome 8 (p12 - p11). Analysis of mRNA from six human cell lines using the p olymerase chain reaction showed the expression of two beta-pol transcr ipts. Sequence analysis revealed that the size difference in these tra nscripts was due to deletion of the 58 bp sequence encoded by exon II, suggesting that the smaller transcript results from an alternative sp licing of the exon II sequence during processing of the beta-pol precu rsor RNA.