Cockayne syndrome group B cellular and biochemical functions

Abstract

The devastating genetic disorder Cockayne syndrome (CS) arises from mutations in the CSA and CSB genes. CS is characterized by progressive multisystem degeneration and is classified as a segmental premature-aging syndrome. The CS complementation group B (CSB) protein is at the interface of transcription and DNA repair and is involved in transcription-coupled and global genome-DNA repair, as well as in general transcription. Recent structure-function studies indicate a process-dependent variation in the molecular mechanism employed by CSB and provide a starting ground for a description of the mechanisms and their interplay.

Figure 1

Summary of CSB cellular phenotypes: the responses of CSB cells to various DNA damaging agents and the underlying cellular processes affected.

Figure 2

Predicted motifs of CSB. A = acidic domain. G = glycine-rich stretch. H = hydrophilic region. N = bipartite NLS. I–VI = ATPase motifs located in the SNF2 domain conserved among the members of the SNF2-like family. NTB = putative NTB motif.

Figure 3

Selected members of the SNF2-like family. Examples of family members from S. cerevisiae, Drosophila melanogaster, and humans (Homo sapiens) are listed. Conserved regions and functionally important motifs are indicated.

Figure 4

Tentative model for CSB function in transcription and TCR. (See text for further explanation.)