High mobility group (HMG) proteins: Modulators of chromatin structure and DNA repair in mammalian cells

• Members of the HMGN family seem to be mainly involved in ‘decompacting’ or loosening up chromatin structure to allow access of repair enzymes and complexes to various types of DNA damage, thereby facilitating and enhancing their repair.
• Members of the HMGA family, on the other hand, appear to primarily be inhibitors of various types of DNA repair, especially when they are aberrantly over-expressed in cells. Two different mechanisms have been advanced to account for such repair inhibition: (i) tight binding of HMGA proteins to altered DNA structures, such as genotoxic DNA lesions, that block access of repair factors to the sites of damage; and, (ii) inhibition of the transcription of specific DNA repair genes as a consequence of HMGA binding to AT-rich regions in their promoter regions.
• The mechanisms by which members of the HMGB family of proteins modulate DNA repair processes are more complex and seem to depend on the particular types of DNA lesions involved and can be either inhibitory or stimulatory in nature.

It has been almost a decade since the last review appeared comparing and contrasting the influences that the different families of High Mobility Group proteins (HMGA, HMGB and HMGN) have on the various DNA repair pathways in mammalian cells. During that time considerable progress has been made in our understanding of how these non-histone proteins modulate the efficiency of DNA repair by all of the major cellular pathways: nucleotide excision repair, base excision repair, double-stand break repair and mismatch repair. Although there are often similar and over-lapping biological activities shared by all HMG proteins, members of each of the different families appear to have a somewhat ‘individualistic’ impact on various DNA repair pathways. This review will focus on what is currently known about the roles that different HMG proteins play in DNA repair processes and discuss possible future research areas in this rapidly evolving field.