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

Indu Kapoor; Abhirup Shaw; Arindam Naha; Elhassan Ali Fathi Emam; Umesh Varshney

doi:10.1016/j.dnarep.2022.103316

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

DNA Repair (Amst). 2022 May:113:103316. doi: 10.1016/j.dnarep.2022.103316. Epub 2022 Mar 4.

Authors

Indu Kapoor¹, Abhirup Shaw¹, Arindam Naha¹, Elhassan Ali Fathi Emam¹, Umesh Varshney²

Affiliations

¹ Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore 560012, India.
² Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore 560012, India; Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore 560064, India. Electronic address: varshney@iisc.ac.in.

PMID: 35306347
DOI: 10.1016/j.dnarep.2022.103316

Abstract

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.

Keywords: Helicases; Lsr2; RNA polymerase; Translocases; UvrB; UvrD2.