“Helicase and Translocase Activities of UvrD:

 A Novel Discovery of DNA Repair Mechanism”

By: .Shahid

Department of Chemistry and Biochemistry, University of Wisconsin-Milwaukee

3210 North Cramer Street, Milwaukee, WI 53211

Advisor: Dr. Arsenio Pacheco

ABSTRACT

DNA damage can directly change the genome via DNA replication. As the DNA helix is the site of transcription and subsequent translation to generate essential protein, so DNA damage can lead several abnormalities and diseases ^[1]. DNA damage occurs constantly because of external factors or chemicals or internal factors. Nucleotide excision repair (NER) is a particularly versatile mechanism in both prokaryotic and eukaryotic cells.  NER removes damaged DNA especially cyclobutene dimer (CPD) induced by ultraviolet light. In E. coli bacteria, the general NER pathway commences when UvrA and UvrB proteins recognize and bind damaged DNA and recruit UvrC to cleave the damage containing strand at specific sites. The resulting oligonucleotide is removed by UvrD, and new oligonucleotide are inserted by DNA polymerase I, using the complementary strand as a template. RNA polymerase (RNAP) block the damaged DNA site during transcription elongation, and thus NER cannot recruit its repair enzymes ^[2,3]. Escherichia coli UvrD binds and slides backward the RNAP along DNA, using its helicase/translocase activity to allow access to the damaged DNA for repair enzymes. This seminar will reveal how the role of UvrD was discovered for NER ^[4]. 

Reference

1. Batty, D. P.&Wood, R. D. Damage recognition in nucleotide excision repair of DNA. Gene 241, 193–204 (2000).
2. Reardon, J. T. & Sancar, A. Nucleotide excision repair. Prog. Nucleic Acid Res. Mol. Biol. 79, 183–235 (2005).
3. VanHouten, B.& McCullough, A. Nucleotide excision repair in E. coli. Ann. NY Acad. Sci. 726, 236–251 (1994).
4. Epshtein V, Kamarthapu V, McGary K, et al. UvrD facilitates DNA repair by pulling RNA polymerase backwards. Nature. 2016.