HMG1 protein stimulates DNA end joining by promoting association of DNA molecules via their ends

High mobility group (HMG) 1 protein is a highly abundant and an evolutionar ily conserved chromosomal protein with two homologous DNA-binding domains ( HMG boxes), A and B, attached by a short basic region to an acidic C-termin al tail. The protein has been implicated in a number of fundamental biologi cal processes including DNA replication, transcription, recombination and r epair. We demonstrate that HMG1 is able to enhance cohesive-end and blunt-e nd DNA ligation by T4 DNA ligase via its B domain. The C-terminal flanking sequence of the B domain (seven basic residues out of approximate to 18) an d a number of conserved amino-acid residues within the HMG box (mainly basi c or hydrophobic) are required for efficient stimulation of ligation. Pull- down assays, electron and scanning force microscopy revealed that HMG1 can associate two DNA molecules via their ends even in the absence of complemen tary overhangs. We propose that HMG1 protein may be involved in the rejoini ng of DNA breaks by different DNA ligases due to its ability to bring DNA d uplexes and their termini into a close proximity while leaving the ends acc essible for ligation.