Xeroderma pigmentosum group F protein binds to Eg5 and is required for proper mitosis: implications for XP‐F and XFE

The xeroderma pigmentosum group F‐cross‐complementing rodent repair deficiency group 1 (XPF‐ERCC1) complex is a structure‐specific endonuclease involved in nucleotide excision repair (NER) and interstrand cross‐link (ICL) repair. Patients with XPF mutations may suffer from two forms of xeroderma pig...

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Published in:Genes to cells : devoted to molecular & cellular mechanisms 2012-03, Vol.17 (3), p.173-185
Main Authors: Tan, Li Jing, Saijo, Masafumi, Kuraoka, Isao, Narita, Takashi, Takahata, Chiaki, Iwai, Shigenori, Tanaka, Kiyoji
Format: Article
Language:English
Subjects:
Aging
Animals
Cell Nucleus - metabolism
DNA Repair
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
Endonuclease
F protein
Gene Knockout Techniques
Growth rate
HEK293 Cells
Humans
Kinesin - genetics
Kinesin - metabolism
Mice
Mitosis
Mutation
Nuclease
Nucleotide excision repair
Photosensitivity
Skin cancer
Spindles
Weaning
Xeroderma pigmentosum
Xeroderma Pigmentosum - genetics
Xeroderma Pigmentosum - metabolism
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Summary:The xeroderma pigmentosum group F‐cross‐complementing rodent repair deficiency group 1 (XPF‐ERCC1) complex is a structure‐specific endonuclease involved in nucleotide excision repair (NER) and interstrand cross‐link (ICL) repair. Patients with XPF mutations may suffer from two forms of xeroderma pigmentosum (XP): XP‐F patients show mild photosensitivity and proneness to skin cancer but rarely show any neurological abnormalities, whereas XFE patients display symptoms of severe XP symptoms, growth retardation and accelerated aging. Xpf knockout mice display accelerated aging and die before weaning. These results suggest that the XPF‐ERCC1 complex has additional functions besides NER and ICL repair and is essential for development and growth. In this study, we show a partial colocalization of XPF with mitotic spindles and Eg5. XPF knockdown in cells led to an increase in the frequency of abnormal nuclear morphology and mitosis. Similarly, the frequency of abnormal nuclei and mitosis was increased in XP‐F and XFE cells. In addition, we showed that Eg5 enhances the action of XPF‐ERCC1 nuclease activity. Taken together, these results suggest that the interaction between XPF and Eg5 plays a role in mitosis and DNA repair and offer new insights into the pathogenesis of XP‐F and XFE.
ISSN:1356-9597
1365-2443
DOI:10.1111/j.1365-2443.2012.01582.x