Transcription coupled nucleotide excision repair (TC-NER) is involved in 
correcting UV-induced damage and other road-blocks encountered in the 
transcribed strand. Mutation frequency decline (Mfd) is a transcription repair 
coupling factor, involved in repair of template strand during transcription. Mfd 
from M. tuberculosis (MtbMfd) is 1234 amino-acids long harboring characteristic 
modules for different activities. Mtbmfd complemented Escherichia coli mfd 
(Ecomfd) deficient strain, enhanced survival of UV irradiated cells and 
increased the road-block repression in vivo. The protein exhibited ATPase 
activity, which was stimulated ∼1.5-fold in the presence of DNA. While the 
C-terminal domain (CTD) comprising amino acids 630 to 1234 showed ∼2-fold 
elevated ATPase activity than MtbMfd, the N-terminal domain (NTD) containing the 
first 433 amino acid residues was able to bind ATP but deficient in hydrolysis. 
Overexpression of NTD of MtbMfd led to growth defect and hypersensitivity to UV 
light. Deletion of 184 amino acids from the C-terminal end of MtbMfd (MfdΔC) 
increased the ATPase activity by ∼10-fold and correspondingly exhibited 
efficient translocation along DNA as compared to the MtbMfd and CTD. 
Surprisingly, MtbMfd was found to be distributed in monomer and hexamer forms 
both in vivo and in vitro and the monomer showed increased susceptibility to 
proteases compared to the hexamer. MfdΔC, on the other hand, was predominantly 
monomeric in solution implicating the extreme C-terminal region in 
oligomerization of the protein. Thus, although the MtbMfd resembles EcoMfd in 
many of its reaction characteristics, some of its hitherto unknown distinct 
properties hint at its species specific role in mycobacteria during 
transcription-coupled repair.