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

• DOI: 10.1126/sciadv.abp9457
• Publication Date: 2022-08-17T17:57:37Z
• Authors: Emmanuel Compe; Evanthia Pangou; Nicolas Le May; Clémence Elly; Cathy Braun; Ji-Hyun Hwang; Frédéric Coin; Izabela Sumara; Kwang-Wook Choi; Jean-Marc Egly
• Keywords: PLK1; Aurora B kinase

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 motor kinesin Eg5 mitotic spindles and midbodies human cells. XPD/Eg5 partnership promoted upon phosphorylation Eg5/T926 by kinase CDK1, conversely, it reduced once Eg5/S1033 phosphorylated NEK6, also targets at T425. does not affect its repair transcription functions, but required for localization, checkpoint activation, chromosome segregation in mitosis. In XPD-mutated cells derived from patient xeroderma pigmentosum, phosphomimetic form XPD/T425D or even nonphosphorylatable Eg5/S1033A specifically restores errors. These results thus highlight phospho-dependent function reveal how defects might contribute XPD-related disorders.