Human Cell Biology Group, Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamada-oka, Suita, Osaka 565-0871, Japan.
Mol Cell. 2010 Aug 27;39(4):632-40. doi: 10.1016/j.molcel.2010.07.029.
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.
着色性干皮病组 D (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。我们发现了一个包含 MMS19 的 XPD 蛋白复合物，该复合物被认为是 TFIIH 的调节剂。然而，MMS19-XPD 复合物不包含 TFIIH 的任何其他亚基。相反，它包含 FAM96B（现在命名为 MIP18）、Ciao1 和 ANT2。MMS19、MIP18 和 XPD 在有丝分裂期间定位于纺锤体。通过 siRNA 介导的 MMS19、MIP18 或 XPD 敲低导致染色体分离不当，并导致具有异常形状的核积累。此外，XP-D 和 XP-D/CS 患者细胞中异常有丝分裂和核的频率增加。这些结果表明，MMS19-XPD 蛋白复合物（现在命名为 MMXD（MMS19-MIP18-XPD））对于正确的染色体分离是必需的，其异常可能导致某些 XP-D 和 XP-D/CS 病例的发病机制。
