MMXD, a TFIIH-Independent XPD-MMS19 Protein Complex Involved in Chromosome Segregation

• Published in: Molecular cell 2010-08, Vol.39 (4), p.632-640
• Main Authors: Ito, Shinsuke, Tan, Li Jing, Andoh, Daisuke, Narita, Takashi, Seki, Mineaki, Hirano, Yasuhiro, Narita, Keiko, Kuraoka, Isao, Hiraoka, Yasushi, Tanaka, Kiyoji
• Format: Article
• Language: English
• Subjects: Adenine Nucleotide Translocator 2 - metabolism; Binding Sites; Carrier Proteins - genetics; Carrier Proteins - metabolism; Cell Nucleus Shape; CELLCYCLE; Chromosome Segregation; DNA; Gene Knockdown Techniques; HCT116 Cells; HeLa Cells; Humans; Metallochaperones - metabolism; Microscopy, Fluorescence; Mitosis; Multiprotein Complexes; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Protein Interaction Domains and Motifs; Protein Interaction Mapping; PROTEINS; RNA Interference; Spindle Apparatus - metabolism; Transcription Factor TFIIH - metabolism; Transcription Factors - genetics; Transcription Factors - metabolism; Transfection; Xeroderma Pigmentosum - genetics; Xeroderma Pigmentosum - metabolism; Xeroderma Pigmentosum - pathology; Xeroderma Pigmentosum Group D Protein - genetics; Xeroderma Pigmentosum Group D Protein - metabolism
• ISSN: 1097-2765; 1097-4164
• 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. [Display omitted] ► Xeroderma pigmentosum group D protein forms a TFIIH-independent protein complex, MMXD ► MMXD subunits localize to the mitotic spindle during mitosis ► Knockdown of MMXD subunits causes improper chromosome segregation and abnormal nuclei ► Abnormal chromosomal segregation is increased in XP-D patient cells