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Phosphorylation of XPD drives its mitotic role independently of its DNA repair and transcription functions

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Compe, Emmanuel | Pangou, Evanthia | Le May, Nicolas | Elly, Clémence | Braun, Cathy | Hwang, Ji-Hyun | Coin, Frédéric | Sumara, Izabela | Choi, Kwang-Wook | Egly, Jean-Marc

Edité par CCSD ; American Association for the Advancement of Science (AAAS) -

International audience. The helicase XPD is known as a key subunit of the DNA repair/transcription factor TFIIH. However, here, we report that XPD, independently to other TFIIH subunits, can localize with the motor kinesin Eg5 to mitotic spindles and the midbodies of human cells. The XPD/Eg5 partnership is promoted upon phosphorylation of Eg5/T926 by the kinase CDK1, and conversely, it is reduced once Eg5/S1033 is phosphorylated by NEK6, a mitotic kinase that also targets XPD at T425. The phosphorylation of XPD does not affect its DNA repair and transcription functions, but it is required for Eg5 localization, checkpoint activation, and chromosome segregation in mitosis. In XPD-mutated cells derived from a patient with xeroderma pigmentosum, the phosphomimetic form XPD/T425D or even the nonphosphorylatable form Eg5/S1033A specifically restores mitotic chromosome segregation errors. These results thus highlight the phospho-dependent mitotic function of XPD and reveal how mitotic defects might contribute to XPD-related disorders.

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