IMP dehydrogenase (IMPDH) catalyzes the rate-limiting step in the de novo synthesis of
guanine, namely the oxidation of
IMP to
XMP with a concomitant reduction of NAD+. In Saccharomyces cerevisiae, a family of four closely-related genes, IMD1,
IMD2 (also known as PUR5), IMD3, and IMD4, encodes the putative IMPDH. Although IMPDH synthesizes
guanine in the cytoplasm, it has also been found in the nucleus, where it associates with
nucleic acids in human cells. Here, we further show that IMPDH is recruited to actively transcribed region of genes. A synthetic lethal screen using a deletion strain of Ctk1
kinase, a yeast homolog of mammalian Cdk9/
P-TEFb that phosphorylates
serine 2 within the
RNA polymerase II (RNApII) C-terminal domain (CTD), identified that
Imd2 genetically interacts with Ctk1. Consistent with this association, IMPDHs were recruited to elongating RNApII only when
serine 2 of the CTD was phosphorylated by Ctk1. Loss of
Imd2 had little effect on the association of most elongation factors with RNApII. However, in cells lacking
Imd2 or all the essential IMPDHs in the presence of minimal
guanine, a defect in the association of Ctk1 with the promoter region was seen. Taken together, our results show that IMPDH is recruited to transcription complex through
serine 2 phosphorylation of RNApII CTD and suggest that it may play a role in initiating transcriptional regulation.