Regulation of DNA-Dependent Activities by the Functional Motifs of the High-Mobility-Group Chromosomal Proteins

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Abstract
The orderly progression of most DNA-related activities such as transcription, replication, recombination, and repair involves changes in the structure of the DNA and in the organization of the chromatin fiber. Some of these structural changes are facilitated by a family of ubiquitous and abundant nonhistone nuclear proteins known as the high-mobility-group (HMG) proteins. In the narrowest traditional sense, the HMG protein family consists of six proteins and is subdivided into three subfamilies: the HMG-1/-2 subfamily, the HMG-I/Y subfamily and the HMG-14/-17 subfamily. These three HMG subfamilies are similar in several physical characteristics (detailed reviews on these proteins are found in references 10, 12, 14, 28, and54); however, each of the subfamilies has a unique protein signature and a characteristic functional sequence motif. These functional sequence motifs are the main site of interaction between the HMG proteins and the DNA or chromatin targets. The HMG-1 domain (often referred to as the HMG-1 box) is the functional motif of the largest HMG subfamily, the HMG-1/-2 proteins; the AT hook is the functional motif of the HMG-I/Y group, and the nucleosomal binding domain is the functional motif of the HMG-14/-17 subfamily. Significantly, all of these functional motifs bind to specific structures in DNA or in chromatin, with little if any specificity for the target DNA sequence. All the HMG proteins are considered to function as architectural elements that modify the structure of DNA and chromatin to generate a conformation that facilitates and enhances various DNA-dependent activities.