Characterization of the mouse Xpf DNA repair gene and differential expression during spermatogenesis

The human XPF protein, an endonuclease subunit essential for DNA excision r epair, may also function in homologous recombination, To investigate a poss ible link between mammalian XPF and recombination that occurs during meiosi s, we isolated, characterized, and determined an expression profile for the mouse Xpf gene. The predicted mouse XPF protein, encoded by a 3.4-kb cDNA, contains 917 amino acids and is 86% identical to human XPF. Appreciable si milarity also exists between mouse XPF and homologous proteins in budding y east (Rad1), fission yeast (Rad16), and fruit fly (Mei-9), all of which hav e dual functions in excision repair and recombination. Sequence analysis of the 38.3-kb Xpf gene, localized to a region in proximal mouse chromosome 1 6, revealed greater than 72% identity to human XPF in 16 regions. Of these conserved elements, 11 were exons and 5 were noncoding sequence within intr ons, Xpf transcript and protein levels were specifically elevated in adult mouse testis. Moreover, increased levels of Xpf and Ercc1 mRNAs correlated with meiotic and early postmeiotic spermatogenic cells. These results suppo rt a distinct role for the XPF/ERCC1 junction-specific endonuclease during meiosis, most likely in the resolution of heteroduplex intermediates that a rise during recombination, (C) 1999 Academic Press.