Queimado L, Rao M, Schultz R A, Koonin E V, Aravind L, Nardo T, Stefanini M, Friedberg E C
Laboratory of Molecular Pathology, Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9072, USA.
Nucleic Acids Res. 2001 May 1;29(9):1884-91. doi: 10.1093/nar/29.9.1884.
The MMS19 gene of the yeast Saccharomyces cerevisiae encodes a polypeptide of unknown function which is required for both nucleotide excision repair (NER) and RNA polymerase II (RNAP II) transcription. Here we report the molecular cloning of human and mouse orthologs of the yeast MMS19 gene. Both human and Drosophila MMS19 cDNAs correct thermosensitive growth and sensitivity to killing by UV radiation in a yeast mutant deleted for the MMS19 gene, indicating functional conservation between the yeast and mammalian gene products. Alignment of the translated sequences of MMS19 from multiple eukaryotes, including mouse and human, revealed the presence of several conserved regions, including a HEAT repeat domain near the C-terminus. The presence of HEAT repeats, coupled with functional complementation of yeast mutant phenotypes by the orthologous protein from higher eukaryotes, suggests a role of Mms19 protein in the assembly of a multiprotein complex(es) required for NER and RNAP II transcription. Both the mouse and human genes are ubiquitously expressed as multiple transcripts, some of which appear to derive from alternative splicing. The ratio of different transcripts varies in several different tissue types.
酿酒酵母的MMS19基因编码一种功能未知的多肽，该多肽是核苷酸切除修复（NER）和RNA聚合酶II（RNAP II）转录所必需的。在此，我们报道了酵母MMS19基因的人类和小鼠直系同源基因的分子克隆。人类和果蝇的MMS19 cDNA均可纠正MMS19基因缺失的酵母突变体中的温度敏感生长和对紫外线杀伤的敏感性，这表明酵母和哺乳动物基因产物之间存在功能保守性。对包括小鼠和人类在内的多种真核生物的MMS19翻译序列进行比对，发现存在几个保守区域，包括靠近C端的一个HEAT重复结构域。HEAT重复序列的存在，以及高等真核生物的直系同源蛋白对酵母突变体表型的功能互补，表明Mms19蛋白在NER和RNAP II转录所需的多蛋白复合物组装中发挥作用。小鼠和人类基因均以多种转录本的形式普遍表达，其中一些转录本似乎来自可变剪接。不同转录本的比例在几种不同的组织类型中有所不同。
