2015
Mechanistic Studies of DNA Repair
Tomas Lindahl, Paul Modrich & Aziz Sancar
About This Prize
The 2015 Nobel Prize in Chemistry was awarded to Tomas Lindahl, Paul Modrich, and Aziz Sancar “for mechanistic studies of DNA repair.” Their work mapped at molecular detail how cells repair damaged DNA to safeguard genetic information. Lindahl discovered base excision repair, Sancar elucidated nucleotide excision repair (the mechanism that fixes UV damage), and Modrich characterized mismatch repair. Together, these pathways protect the genome from tens of thousands of DNA lesions occurring daily in each cell.
Aziz Sancar
“Mechanisms of DNA Repair by Photolyase and Excision Nuclease”
Paul Modrich
“Mechanisms in E. coli and Human Mismatch Repair”
Tomas Lindahl
“The Intrinsic Fragility of DNA”
Key Concepts
- • Base Excision Repair (BER): Repair of small base lesions by glycosylases; handles ~20,000 lesions per cell per day
- • Nucleotide Excision Repair (NER): Removal of bulky helix-distorting lesions including UV-induced pyrimidine dimers
- • Mismatch Repair (MMR): Correction of replication errors; defects cause hereditary nonpolyposis colorectal cancer (Lynch syndrome)
- • Photolyase: Light-activated enzyme that directly reverses UV-induced cyclobutane pyrimidine dimers