MMXD, a TFIIH-Independent XPD-MMS19 Protein Complex Involved in Chromosome Segregation
MMXD, a TFIIH-Independent XPD-MMS19 Protein Complex Involved in Chromosome Segregation
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DOI：
10.1016/j.molcel.2010.07.029
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发表时间：
2010-08-27
期刊：
影响因子：
16
通讯作者：
Tanaka, Kiyoji
中科院分区：
文献类型：
--
作者：
Ito, Shinsuke;Tan, Li Jing;Tanaka, Kiyoji
着色性干皮病D组（XPD）蛋白是TFIIH的亚基之一，是核苷酸切除修复和转录所必需的。我们发现含有MMS19的XPD蛋白复合物被认为是TFIIH的调节因子。然而，MMS19-XPD复合物不含TFIIH的任何其他亚基。相反，它包括FAM96B（现在指定为MIP18）、Ciao1和ANT2。MMS19， MIP18和XPD在有丝分裂时定位于纺锤体。sirna介导的MMS19、MIP18或XPD的敲低导致染色体分离不当和细胞核形状异常的积累。此外，XP-D和XP-D/CS患者细胞有丝分裂和细胞核异常频率增加。这些结果表明，MMS19-XPD蛋白复合体，现在被命名为MMXD (MMS19-MIP18-XPD)，是染色体正确分离所必需的，其异常可能导致某些XP-D和XP-D/CS的发病。
Xeroderma pigmentosum group D (XPD) protein is one of the subunits of TFIIH that is required for nucleotide excision repair and transcription. We found a XPD protein complex containing MMS19 that was assumed to be a regulator of TFIIH. However, the MMS19-XPD complex did not contain any other subunits of TFIIH. Instead, it included FAM96B (now designated MIP18), Ciao1, and ANT2. MMS19, MIP18, and XPD localized to the mitotic spindle during mitosis. The siRNA-mediated knockdown of MMS19, MIP18, or XPD led to improper chromosome segregation and the accumulation of nuclei with abnormal shapes. In addition, the frequency of abnormal mitosis and nuclei was increased in XP-D and XP-D/CS patients' cells. These results indicate that the MMS19-XPD protein complex, now designated MMXD (MMS19-MIP18-XPD), is required for proper chromosome segregation, an abnormality of which could contribute to the pathogenesis in some cases of XP-D and XP-D/CS.