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Xeroderma pigmentosum group F protein binds to Eg5 and is required for proper mitosis: implications for XP‐F and XFE
Author(s) -
Tan Li Jing,
Saijo Masafumi,
Kuraoka Isao,
Narita Takashi,
Takahata Chiaki,
Iwai Shigenori,
Tanaka Kiyoji
Publication year - 2012
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/j.1365-2443.2012.01582.x
Subject(s) - xeroderma pigmentosum , biology , mitosis , nucleotide excision repair , ercc1 , dna repair , dna damage , microbiology and biotechnology , cancer research , genetics , dna
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.