The Nobel Prize in Chemistry 2015: Exciting discoveries in DNA repair by Aziz Sancar.

David K Orren

doi:10.1007/s11427-015-4994-1

Abstract

On October 7, 2015, the Nobel Prize in Chemistry for 2015 was awarded to three deserving scientists for their pioneering research on DNA repair. Tomas Lindahl was recognized for studies that uncovered the inherent instability of DNA as well as the mechanism of the base excision repair pathway, Paul Modrich for characterization of the mismatch repair pathway, and Aziz Sancar for mechanistic elucidation of the nucleotide excision repair (NER) pathway. For me, the announcement of these awards in my area of research was extremely gratifying, particularly so because Aziz was my mentor during my Ph.D. studies that examined the steps of prokaryotic NER. Memorably, I trained in the Sancar laboratory at a time where groundbreaking discoveries were being made in the burgeoning field of DNA repair, and can personally attest to his dedication and keen intellect. The text below primarily addresses Aziz’s critical contributions towards our understanding of NER processes in E. coli during the early years of study on this pathway. Other researchers have made important contributions in this area that may not be specified or cited here due to emphasis and space constraints of this article. CONTRIBUTIONS TO UNDERSTANDING PROKARYOTIC NER: BIOCHEMICAL CHARACTERIZATION AND RECONSTITUTION OF NER PROCESSES

Highlights

On October 7, 2015, the Nobel Prize in Chemistry for 2015 was awarded to three deserving scientists for their pioneering research on DNA repair
Tomas Lindahl was recognized for studies that uncovered the inherent instability of DNA as well as the mechanism of the base excision repair pathway, Paul Modrich for characterization of the mismatch repair pathway, and Aziz Sancar for mechanistic elucidation of the nucleotide excision repair (NER) pathway
While UvrB’s presence in the incision complex is required, subsequent experiments clarified that the 5′ and 3′ incisions were catalyzed by separate domains within UvrC (Lin and Sancar, 1992; Verhoeven et al, 2000). These findings suggested that the dual incision events characteristic of NER in E. coli occurred through an ordered series of steps; theoretically, this sequential mechanism ensures specificity for initiating removal of DNA adducts while minimizing incision of undamaged DNA