A Brief Note On Protein-DNA Interactions

SOPHIA COLLEGE

Protein-DNA Interaction

MAYUR GAIKWAD

05/05/2015

INTRODUCTION

Protein–DNA interactions play a major role in all fields of genetics from regulation and transcription of individual genes to repair of damaged sequences, even to the stabilization of DNA in chromatin and the replication of entire genomes. It is estimated that 2–3% of prokaryotic and 6–7% of eukaryotic genes code for DNA-binding proteins. Additionally, many of these proteins do not merely bind DNA, but also interact with other proteins and sometimes, as is shown in the example of RNA polymerase, only display theirfull activity when organized in multimeric complexes.

SEQUENCE-SPECIFIC DNA BINDING

Protein recognition of specific sequences on the DNA double

One of the great challenges of systems biology is to translate and summarize this vast amount of information in so-called regulatory networks that can be simulated in computational models . The long-term goal is to be able to simulate and ultimately predict the responses of cells and organism to a changing environment. In order to construct regulatory networks, the system can be divided into three organizational levels. The lowest level is represented by the interactions of one single element (transcription factor) with its target DNA promoter . This interaction can either activate or repress the expression of the downstream gene(s). In many, but not all, cases is the DNA-binding activity of the transcription factor itself that is regulated, for instance by binding of a small molecule or even a single atom such as iron. The next level is composed of certain network motifs where the single transcriptions factor is part of a regulatory module. Three examples of such motifs are depicted in Fig. 24.9 B. The single-input module (SIM) consists of one transcription factor that controls a number of genes. The feed-forward loop (FFL) is represented by one transcription factor that activates the expression of another transcription factor. Regulons are characterized by several transcription

The great importance of these interactions stems from the fact that DNA-binding transcription factors are central switches of a cell’s regulatory network. The transcription factor SRY, for instance, is sufficient to trigger the development of the male sex. Mutations in the protein can lead to a sex change of affected embryos. A number of hormone receptors like the glucocorticoid or estrogen receptor are zinc finger proteins, which play an important part in hormone-controlled metabolism. Finally, cancer can also be caused by mutated transcription factors. The proteins Jun and Fos are well-studied leucine zipper proteins that do not only have to bind the correct promoter sequences, but can only fulfill this physiological function as a Jun/Fos protein complex. These proteins are of great medical importance since mutations in the underlying genes have been linked to the development of certain