Switch regions, which are the regions undergoing DNA rearrangement during class switch recombination are unique in their sequences. Tandem repeats with runs of guanines are hallmarks of switch regions. I am interested in the structural potential of these repeats to form G- quadruplexes upon transcription and their significance in recruiting novel repair functions. My current investigations center on the role played by human exonuclease1 (hEXO1), which is the 5'-3' exonuclease in mismatch repair and also has 5'flap endonuclease activity. Cloned fragments of the murine Sγ3 and synthetic Sμ switch region sequences were seen to trigger 5'-3' exonuclease activity by hEXO1 when transcribed from the T7 promoter. Interestingly, this activity was transcription and orientation dependent, meaning that formation of G quadruplex structures on the non- template strand was necessary for this novel activity. This could redefine the role of hEXO1 in CSR, apart from its activity in mismatch repair and prove to be another variable in creating breaks in Ig genes. I am also interested in the biophysical properties of G- rich repetitive DNA, which are hallmarks of switch regions, minisatellites, some promoters as well as proto-oncogenes, which can tell us more about the dynamics of these regions in the genome and their evolution.
