MMXD, a TFIIH-independent XPD-MMS19 protein complex involved in chromosome segregation.
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.
Ito
Shinsuke
S
Human Cell Biology Group, Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamada-oka, Suita, Osaka 565-0871, Japan.
Tan
Li Jing
LJ
Andoh
Daisuke
D
Narita
Takashi
T
Seki
Mineaki
M
Hirano
Yasuhiro
Y
Narita
Keiko
K
Kuraoka
Isao
I
Hiraoka
Yasushi
Y
Tanaka
Kiyoji
K
D033742:Adenine Nucleotide Translocator 2 / Q000378:metabolism; D001665:Binding Sites; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D053144:Cell Nucleus Shape; D020090:Chromosome Segregation; D055785:Gene Knockdown Techniques; D045325:HCT116 Cells; D006367:HeLa Cells; D006801:Humans; D056511:Metallochaperones / Q000378:metabolism; D008667:Metalloproteins; D008856:Microscopy, Fluorescence; D008938:Mitosis; D046912:Multiprotein Complexes; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D054730:Protein Interaction Domains and Motifs; D025941:Protein Interaction Mapping; D034622:RNA Interference; D008941:Spindle Apparatus / Q000378:metabolism; D051758:Transcription Factor TFIIH / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014983:Xeroderma Pigmentosum / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics / Q000378:metabolism*
D033742:Adenine Nucleotide Translocator 2; C112111:CIAO1 protein, human; C569498:CIAO2B protein, human; D002352:Carrier Proteins; C416322:MMS19 protein, human; D056511:Metallochaperones; D008667:Metalloproteins; D046912:Multiprotein Complexes; D009687:Nuclear Proteins; D014157:Transcription Factors; D051758:Transcription Factor TFIIH; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human