Identification and characterization of a paralog of human cell cycle checkpoint gene HUS1
Identification and characterization of a paralog of human cell cycle checkpoint gene HUS1
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DOI：
10.1006/geno.2002.6737
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发表时间：
2002-04-01
期刊：
影响因子：
4.4
通讯作者：
Lieberman, HB
中科院分区：
文献类型：
--
作者：
Hang, HY;Zhang, YZ;Lieberman, HB
人类细胞周期检查点基因HUS1B的同源基因已被鉴定并命名为HUS1B。它编码一个278个氨基酸的蛋白质，与HUS1有48%的同源性和69%的相似性。BLAST搜索也检测到了HUS1B的小鼠和大鼠的同源物。HUS1B在许多人体组织中有不同程度的表达，观察到的组织特异性水平与HUS1相似。HUS1-RAD1-RAD9蛋白复合体被认为形成一种增殖细胞核抗原(PCNA)样结构，对细胞周期检查点功能至关重要。然而，HUS1B直接与RAD1相互作用，而不与RAD9或HUS1相互作用，而HUS1可以与RAD1、RAD9和HUS1的另一个分子结合，这表明HUS1B不能简单地替代HUS1在复合体中的作用。HUS1B在进化上不如HUS1保守。此外，在人类细胞中过表达HUS1B而不是HUS1B可诱导克隆性细胞死亡。我们认为，HUS1B和HUS1在调节细胞周期检查点和基因组完整性方面具有不同但相关的作用。
A paralog of the human cell cycle checkpoint gene HUSI has been identified and designated HUS1B. It encodes a 278-amino-acid protein, 48% identical and 69% similar to HUS1. Mouse and rat orthologs of HUS1B have also been detected by a BLAST search. HUS1B is expressed variably in many human tissues, and the tissue-specific levels observed parallel those for HUS1. A HUS1-RAD1-RAD9 protein complex is thought to form a proliferating cell nuclear antigen (PCNA)-like structure, important for cell cycle checkpoint function. However, HUS1B directly interacts with RAD1, but not RAD9 or HUS1, whereas HUS1 can bind RAD1, RAD9, and another molecule of HUS1, suggesting that HUS1B cannot simply substitute for HUS1 in the complex. HUS1B is less conserved evolutionarily than HUS1. Furthermore, overexpression of HUS1B but not HUSI in human cells induces clonogenic cell death. We suggest that HUS1B and HUS1 have distinct but related roles in regulating cell cycle checkpoints and genomic integrity.