Shannon M, Lamerdin J E, Richardson L, McCutchen-Maloney S L, Hwang M H, Handel M A, Stubbs L, Thelen M P
Molecular and Structural Biology Division, Lawrence Livermore National Laboratory, Livermore, California 94550, USA.
Genomics. 1999 Dec 15;62(3):427-35. doi: 10.1006/geno.1999.6016.
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.
人类XPF蛋白是DNA切除修复所必需的一种核酸内切酶亚基，它也可能在同源重组中发挥作用。为了研究哺乳动物XPF与减数分裂过程中发生的重组之间可能存在的联系，我们分离、鉴定并确定了小鼠Xpf基因的表达谱。由一个3.4 kb的cDNA编码的预测小鼠XPF蛋白含有917个氨基酸，与人类XPF的同源性为86%。小鼠XPF与芽殖酵母（Rad1）、裂殖酵母（Rad16）和果蝇（Mei-9）中的同源蛋白之间也存在明显的相似性，它们在切除修复和重组中都具有双重功能。定位在小鼠近端16号染色体区域的38.3 kb Xpf基因的序列分析显示，在16个区域中与人类XPF的同源性超过72%。在这些保守元件中，11个是外显子，5个是内含子中的非编码序列。Xpf转录本和蛋白水平在成年小鼠睾丸中特异性升高。此外，Xpf和Ercc1 mRNA水平的升高与减数分裂期和减数分裂后早期的生精细胞相关。这些结果支持了XPF/ERCC1连接特异性核酸内切酶在减数分裂过程中具有独特作用，最有可能是在重组过程中出现的异源双链中间体的拆分中发挥作用。
