Human Rad50 is physically associated with human Mre11: identification of a conserved multiprotein complex implicated in recombinational DNA repair
Human Rad50 is physically associated with human Mre11: identification of a conserved multiprotein complex implicated in recombinational DNA repair
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DOI：
10.1128/mcb.16.9.4832
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发表时间：
1996-09
影响因子：
5.3
通讯作者：
G. Dolganov;R. Maser;A. Novikov;L. Tosto;Su-Jin Chong;D. Bressan;J. Petrini
中科院分区：
文献类型：
--
作者：
G. Dolganov;R. Maser;A. Novikov;L. Tosto;Su-Jin Chong;D. Bressan;J. Petrini
在这份报告中，我们描述了人类Rad50同源基因hRAD50的鉴定和分子特征。HRAD50包括在通过关注跨越5q23到5q31的染色体间隔的直接cDNA选择策略分离的cDNA集合中。5q23-q31间期改变常见于骨髓异常增生症和髓系白血病。因此，采取了这一战略，以创建该区域的详细遗传图谱。酿酒酵母RAD50(ScRAD50)是三个酵母RAD52上位型成员之一(ScRAD50、ScMRE11和ScXRS2)，在有丝分裂细胞中，突变消除了减数分裂重组，但赋予了高度重组表型。酵母Rad50、Mre11和Xrs2蛋白似乎在一个多蛋白复合体中发挥作用，这与观察到相应的突变体提供基本上相同的表型是一致的。在这份报告中，我们证明了人的Rad50和Mre11蛋白稳定地结合在一个蛋白质复合体中，该复合体可能包括其他三种蛋白质。HRAD50在所有被检测的组织中都有表达，但在睾丸中的mRNA水平显著高于其他组织。其他人类RAD52上位组同源基因也表现出这种表达模式，提示人类RAD52上位组蛋白参与减数分裂重组。人类RAD52上位组蛋白高度保守，作用于与酵母相似的蛋白质复合体中。这些发现表明，RAD52上位组的功能在人类细胞中是保守的。
In this report, we describe the identification and molecular characterization of a human RAD50 homolog, hRAD50. hRAD50 was included in a collection of cDNAs which were isolated by a direct cDNA selection strategy focused on the chromosomal interval spanning 5q23 to 5q31. Alterations of the 5q23-q31 interval are frequently observed in myelodysplasia and myeloid leukemia. This strategy was thus undertaken to create a detailed genetic map of that region. Saccharomyces cerevisiae RAD50 (ScRAD50) is one of three yeast RAD52 epistasis group members (ScRAD50, ScMRE11, and ScXRS2) in which mutations eliminate meiotic recombination but confer a hyperrecombinational phenotype in mitotic cells. The yeast Rad50, Mre11, and Xrs2 proteins appear to act in a multiprotein complex, consistent with the observation that the corresponding mutants confer essentially identical phenotypes. In this report, we demonstrate that the human Rad50 and Mre11 proteins are stably associated in a protein complex which may include three other proteins. hRAD50 is expressed in all tissues examined, but mRNA levels are significantly higher in the testis. Other human RAD52 epistasis group homologs exhibit this expression pattern, suggesting the involvement of human RAD52 epistasis group proteins in meiotic recombination. Human RAD52 epistasis group proteins are highly conserved and act in protein complexes that are analogous to those of their yeast counterparts. These findings indicate that the function of the RAD52 epistasis group is conserved in human cells.