Abstract

NEIL1/Glycosylase/BER/Splicing variant/Mouse. Oxidized pyrimidines are mainly repaired by base excision repair, which is initiated by damage-specific DNA glycosylases. NEIL1, the mammalian homolog of Escherichia coli endonuclease VIII and a major DNA glycosylase, initiates repair of oxidized pyrimidines. Here, we investigated the expression of two putative variant mouse NEIL1 (mNEIL1) mRNAs—variant 1 (“Neil1 protein ” mRNA; BC043297 in the NCBI database) and variant 2 (“unnamed protein ” mRNA; AK040802 in the NCBI database)—in nor-mal mouse organs. Reverse transcription-PCR showed that both mRNAs were expressed in total RNA samples from 9 organs. Immunoblot analysis of a nuclear extract from normal mouse liver revealed three bands corresponding to full-length mNEIL1 protein and the two predicted variant proteins. However, nei-ther variant protein, which included an N-terminal enzymatic activity domain deduced from the mRNA variants, were enzymatically active under multiple reaction conditions when expressed as his-tagged recombinant proteins. Nevertheless, recombinant variant 1 protein influenced mNEIL1 activity, while recombinant variant 2 protein had no influence. These results suggest that mNEIL1 mRNA variants are expressed in a variety of organs in normal mice and that variant 1 protein may regulate mNEIL1 activity.