Role of the nucleotide excision repair pathway proteins (UvrB and UvrD2) in recycling UdgB, a base excision repair enzyme in Mycobacterium smegmatis

Cross-talks between DNA repair pathways are emerging as a crucial strategy in the maintenance of the genomic integrity. A double-stranded (ds) DNA specific DNA glycosylase, UdgB is known to excise uracil, hypoxanthine and ethenocytosine. We earlier showed that Mycobacterium smegmatis (Msm) UdgB stays back on the AP-sites it generates in the DNA upon excision of the damaged bases. Here, we show that in an Msm strain deleted for a nucleotide excision repair (NER) protein, UvrB (uvrB(-)), UdgB expression is toxic, and its deletion from the genome (udgB-) rescues the strain from the genotoxic stress. However, UdgB bound AP-site is not a direct substrate for NER in vitro. We show that UvrD2 and UvrB, known helicases with single-stranded (ss) DNA translocase activity, facilitate recycling of UdgB from AP-DNA. Our studies reveal that the helicases play an important role in exposing the AP-sites in DNA and make them available for further repair.

Automated summary

Cross-talks between DNA repair pathways are crucial for maintaining genomic integrity. In this study, we found that the AP-sites bound by UdgB are not direct substrates for nucleotide excision repair (NER) and that helicases UvrD2 and UvrB facilitate the recycling of UdgB from AP-DNA, exposing the AP-sites for further repair.