Characterization of the mouse Xpf DNA repair gene and differential expression during spermatogenesis.
The human XPF protein, an endonuclease subunit essential for DNA excision repair, may also function in homologous recombination. To investigate a possible link between mammalian XPF and recombination that occurs during meiosis, 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 similarity also exists between mouse XPF and homologous proteins in budding yeast (Rad1), fission yeast (Rad16), and fruit fly (Mei-9), all of which have dual functions in excision repair and recombination. Sequence analysis of the 38.3-kb Xpf gene, localized to a region in proximal mouse chromosome 16, revealed greater than 72% identity to human XPF in 16 regions. Of these conserved elements, 11 were exons and 5 were noncoding sequence within introns. 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 support a distinct role for the XPF/ERCC1 junction-specific endonuclease during meiosis, most likely in the resolution of heteroduplex intermediates that arise during recombination.
Shannon
M
M
Molecular and Structural Biology Division, Lawrence Livermore National Laboratory, Livermore, California 94550, USA.
Lamerdin
J E
JE
Richardson
L
L
McCutchen-Maloney
S L
SL
Hwang
M H
MH
Handel
M A
MA
Stubbs
L
L
Thelen
M P
MP
D000595:Amino Acid Sequence; D000818:Animals; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D004260:DNA Repair; D018076:DNA, Complementary / Q000032:analysis; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics*; D004720:Endonucleases; D015870:Gene Expression; D005854:Germ Cells / Q000378:metabolism; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009928:Organ Specificity / Q000235:genetics; D011506:Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013091:Spermatogenesis / Q000235:genetics*; D013737:Testis / Q000378:metabolism
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D011506:Proteins; C095888:xeroderma pigmentosum group F protein; D004720:Endonucleases; C499360:Ercc1 protein, mouse