Evidence for intrinsic DNA bends within the human cdc2 promoter

Abstract

Cyclin-dependent protein kinases (Cdks) are key regulatory proteins of the eukaryotic cell cycle. The product of the cdc2 gene, p34 cdc2 (cdk1), is the catalytic subunit of a serine/threonine protein kinase that is expressed in S phase and functions in the G2 to M phase transition. Previous studies indicate that the human cdc2 gene expression is dependent on cell growth, and is transcriptionally regulated in a complex manner involving multiple transcription factors binding to specific sites in the promoter. One possible mechanism by which these transcription factors regulate transcription is that by binding to their cognate sites they induce bends in the DNA helix, thereby allowing their interaction with the basal transcription machinery through protein-protein contacts. Such protein-induced DNA bending is also influenced by intrinsic bends in the regulatory region. Using both theoretical and experimental approaches, the study reports that the human cdc2 promoter has an intrinsic DNA bend with a broad locus of curvature.