HRAD30A, a Gene Encoding a Class Y Low-Fidelity Dna Polymerase Has a Low Complexity Region in Intron I Associated with Tissue-Specific Alternative Splicing

. The XP Variant (XPV) is a complementation group of the human disease xeroderma pigmentosum that was recently identified as a caused by mutations in a gene that maps to 6p21, hRad30A, that encodes a novel DNA polymerase, pol η[1,2]. Pol η is a member of a large family, class Y, of low-fidelity DNA polymerases. It has the unusual property that although it can replicate UV-induced pyrimidine dimers in vivo with the insertion of the correct bases in the daughter strand, in vitro it is very error-prone and inserts mutagenic bases at about 1% frequency[3,4]. We recently identified an alternative splice variant of hRad30A mRNA in the testis and fetal liver, suggesting that there may be tissue-specific regulation of this gene[5]. This alternative splicing results in the elimination of exon II that contains the ATG start site for transcription and results in a cDNA that does not complement the XPV defect[5].