Human and mouse homologs of the Saccharomyces cerevisiae RAD54 DNA repair gene: Evidence for functional conservation
Human and mouse homologs of the Saccharomyces cerevisiae RAD54 DNA repair gene: Evidence for functional conservation
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DOI：
10.1016/s0960-9822(02)00606-1
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发表时间：
1996-07-01
期刊：
影响因子：
9.2
通讯作者：
Hoeijmakers, JHJ
中科院分区：
文献类型：
--
作者：
Kanaar, R;Troelstra, C;Hoeijmakers, JHJ
工作背景：同源重组在生殖细胞和体细胞中都具有重要意义，前者在减数分裂过程中产生遗传多样性，后者保护DNA免受遗传毒性损伤。在酵母酿酒酵母中，这些过程需要遗传上明确定义的RAD 52途径。已经在哺乳动物中鉴定出与RAD 52组中的那些基因相似的基因。II是不知道这种保守的主要序列是否延伸到保守的functions.Results：在这里，我们报告的cDNA编码的人和小鼠的同源物的RAD 54的分离。人（hHR54）和小鼠（mHR54）蛋白与Rad54有48%的同一性，属于SNF2/SWI2家族，其特征在于DNA依赖性ATP酶中发现的氨基酸基序。hHR54基因定位于染色体1p32，hHR54蛋白定位于细胞核。我们发现hHR 54 mRNA水平在G1期晚期增加，与Baeri发现的RAD 54 mRNA一样。mHR 54 mRNA水平在生殖细胞和淋巴发育器官中升高，并且mHR 54表达的增加与精子发生的减数分裂阶段相关。结论：mHR 54的组织特异性表达与其在重组中的作用一致，互补实验表明，从酵母到人类，Rad54的DNA修复功能是保守的，我们的发现强调了DNA修复途径的重要性：尽管它们是复杂的，涉及多种蛋白质，但它们似乎在真核生物界中功能上是保守的。
Background: Homologous recombination is at eminent importance both in germ cells, to generate genetic diversity during meiosis, and in somatic cells, to safeguard DNA:rom genotoxic damage. The genetically well-defined RAD52 pathway is required for these processes in the yeast Saccharomyces cerevisiae, Genes similar to those in the RAD52 group have been identified in mammals. Ii is not known whether this conservation of primary sequence extends to conservation of function.Results: Here we report the isolation of cDNAs encoding a human and a mouse homolog of RAD54. The human (hHR54) and mouse (mHR54) proteins were 48% identical to Rad54 and belonged to the SNF2/SWI2 family, which is characterized by amino-acid motifs found in DNA-dependent ATPases. The hHR54 gene was mapped to chromosome 1p32, and the hHR54 protein was located in the nucleus. We found that the levels of hHR54 mRNA increased in late G1 phase, as has baeri found for RAD54 mRNA. The level of mHR54 mRNA was elevated in organs of germ cell and lymphoid development and increased mHR54 expression correlated with the meiotic phase of spermatogenesis. The hHR54 cDNA could partially complement the methyl methanesulfonate-sensitive phenotype oi SI cerevisiae rad54 Delta cells.Conclusions: The tissue-specific expression of mHR54 is consistent with a role for the gene in recombination, The complementation experiments show that the DNA repair function of Rad54 is conserved from yeast to humans, Our findings underscore he fundamental importance of DNA repair pathways: even though they are complex and involve multiple proteins, they seem to he functionally conserved throughout;he eukaryotic kingdom.