Disease relevance of hay

• The haywire gene of Drosophila encodes a protein with 66% identity to the product of the human ERCC3 gene, associated with xeroderma pigmentosum B (XP-B) and Cockayne's syndrome (CS) [1].

High impact information on hay

• Phenotypes of haywire mutants mimic some of the effects of XP [1].
• Vertebrate Cdk7 is also known to be part of TFIIH [2].
• Interacting genes that affect microtubule function: the nc2 allele of the haywire locus fails to complement mutations in the testis-specific beta-tubulin gene of Drosophila [3].
• Cyclin-dependent kinase (CDK)7-cyclin H, the CDK-activating kinase (CAK) and TFIIH-associated kinase in metazoans can be activated in vitro through T-loop phosphorylation or binding to the RING finger protein MAT1 [4].
• TFIIH has been implicated in several fundamental cellular processes, including DNA repair, cell cycle progression, and transcription [5].

Biological context of hay

• In order to investigate this question we tested whether mutations in the Drosophila XPB homolog, haywire (hay), would modify homeotic derepression phenotypes [6].
• Here we show that the Drosophila TFIIH component Xpd negatively regulates the cell cycle function of Cdk7, the CAK activity [7].
• TFIIH trafficking and its nuclear assembly during early Drosophila embryo development [8].
• Thus phosphorylation on Thr170 could provide a mechanism to augment CTD phosphorylation by TFIIH-associated CDK7, and thereby regulate transcription [4].

Anatomical context of hay

• We found that the TFIIH core is initially located in the cytoplasm of syncytial blastoderm embryos, and that after mitotic division ten and until the cellular blastoderm stage, the core moves from the cytoplasm to the nucleus [8].
• These phenotypes are consistent with a role for the haywire gene product in general microtubule function [3].

Physical interactions of hay

• Cdk7 is also found in the transcription factor complex TFIIH, suggesting that it participates in vivo in the control of RNA polymerase II [9].

Regulatory relationships of hay

• This study significantly extends the role of p52 in regulating XPB ATPase activity and, consequently, both its transcriptional and nucleotide excision repair functions [10].

Other interactions of hay

• Sequence analysis of lethal haywire alleles revealed the importance of the nucleotide-binding domain, suggesting an essential role for ATPase activity [11].
• The recessive male sterile mutation haync2 of Drosophila melanogaster fails to complement certain beta 2-tubulin and alpha-tubulin mutations, suggesting that the haywire product plays a role in microtubule function, perhaps as a structural component of microtubules [12].

References