Cell cycle regulation and functions of HMG-I(Y).

Abstract

Members of the HMG-I(Y) family of "high mobility group" (HMG) proteins are distinguished from other nonhistone chromatin proteins by their ability to preferentially recognize the structure of the narrow minor groove of A.T-sequences of B-form DNA. In vivo the HMG-I(Y) proteins are localized in the A.T-rich G/Q bands and in the "scaffold-associated regions" (SARs) of metaphase chromosomes. These proteins also share with some of the other "HMG box" proteins the ability to recognize non-B-form structures, such as cruciforms (four-way junctions), as well as the possessing the capacity to introduce both bends and supercoils in substrate DNAs. These characteristics, along with their ability to specifically interact with a number of known transcription factors, enable the HMG-I(Y) proteins to function in vivo as structural transcription factors for a number mammalian genes. The HMG-I(Y) proteins are also in vivo substrates for the cell cycle regulated Cdc2 kinase which phosphorylates the DNA-binding domain(s) of the protein and, as a result, decreases their substrate binding affinity. This reversible in vivo pattern of Cdc2 kinase phosphorylations during the cell cycle is likely to play a major role in mediating the biological function(s) of the HMG-I(Y) proteins.