Disease relevance of Xpd

• Increased UV light sensitivity in transgenic Drosophila expressing the antisense XPD homolog [1].
• Mutations in the XPD gene generate the cancer-prone syndrome xeroderma pigmentosum, Cockayne's syndrome, and trichothiodystrophy [1].

High impact information on Xpd

• Distribution analysis in polytene chromosomes shows that DmXPD is highly concentrated in the interbands, especially in the highly transcribed regions known as puffs [2].
• In embryos at the syncytial blastoderm stage, DmXPD is cytoplasmic [2].
• UV-light irradiation of third-instar larvae induces an increase in the signal intensity and in the number of sites where the DmXPD protein is located in polytene chromosomes, indicating that the DmXPD protein is recruited intensively in the chromosomes as a response to DNA damage [2].
• At the onset of transcription in somatic cells and during gastrulation in germ cells, DmXPD moves to the nuclei [2].
• In addition, we present evidence that suggests that DNA helicase subunits XPB and XPD are assembled in the core when they are transported into the nucleus and are required for the onset of transcription [3].

Biological context of Xpd

• Simultaneously, the downregulation of Xpd might be a major mechanism of mitotic silencing of basal transcription [4].
• Downregulation of Xpd thus seems to contribute to the upregulation of mitotic CAK activity and to regulate mitotic progression positively [4].
• Excess Xpd titrates CAK activity, resulting in decreased Cdk T-loop phosphorylation, mitotic defects and lethality, whereas a decrease in Xpd results in increased CAK activity and cell proliferation [4].
• Here we show that the Drosophila TFIIH component Xpd negatively regulates the cell cycle function of Cdk7, the CAK activity [4].
• The XPD gene is required for excision repair of UV-damaged DNA and is an important component of nucleotide excision repair (NER) [1].

Other interactions of Xpd

• This is an expected phenotype if the XPD function is affected and indicates that the antisense approach may be an alternative in the study of TFIIH functions in Drosophila [1].

References