2015 Nobel Prize in Chemistry
Reason for Award
for mechanistic studies of DNA repair
Laureates
Sweden, 
United Kingdom of Great Britain and Northern Ireland
United States of America
United States of America, 
Turkey
Explanation
The DNA inside our bodies is like a huge instruction manual. Sunlight’s UV rays and normal chemical reactions can damage it every day. Tomas Lindahl, Paul Modrich and Aziz Sancar discovered how cells cleverly fix those scratches. It is similar to a skilled toy-maker replacing broken parts so the toy works again. Thanks to these repairs, we stay healthy for a long time. Their discoveries also give doctors ideas for new cancer treatments.
Related Keywords
DNA repair
DNA repair refers to all cellular reactions that detect and fix DNA damage. Multiple pathways, such as base-excision, nucleotide-excision and mismatch repair, operate in parallel. They lower mutation rates and maintain genome stability. Distinct enzyme assemblies are recruited depending on lesion type. Cancer therapy sometimes exploits these pathways by inhibiting repair in tumor cells.
base excision repair
Base excision repair principally removes chemically modified single bases. A DNA glycosylase excises the damaged base and an AP endonuclease nicks the backbone. DNA polymerase inserts the correct nucleotide and a ligase seals the strand. Two sub-pathways exist: short-patch (1 nt) and long-patch (2–10 nt). It is essential for countering oxidative or deamination damage.
nucleotide excision repair
Nucleotide excision repair removes bulky DNA distortions caused by UV light or chemical carcinogens. A recognition complex detects the lesion and makes dual incisions excising a 12–30-nt oligomer. DNA polymerase fills the gap and ligase seals it. In humans, more than 30 proteins, including XPA–XPG, cooperate. Defects cause extreme sun-sensitivity disorders such as xeroderma pigmentosum.
mismatch repair
Mismatch repair corrects wrongly paired bases introduced during replication. MutS detects the mismatch and MutL transmits the signal to nick the nascent strand. An exonuclease removes the error region, and DNA polymerase plus ligase resynthesize the correct strand. Defects in humans underlie hereditary colorectal cancer. MMR-deficient tumors have high mutation loads and respond well to immunotherapy.
genome stability
Genome stability denotes a cell’s ability to maintain accurate genetic information. DNA repair, replication checkpoints and chromosome segregation collaborate to preserve it. When stability falters, mutations and chromosomal aberrations accumulate. This accelerates ageing and elevates cancer risk. Studying repair pathways provides the foundation for understanding genome stability mechanisms.
mutation
A mutation is a permanent change in DNA sequence. It can confer advantages or cause disease. When repair systems fail, mutation rates rise dramatically. UV light and chemicals are classic mutation inducers. Cancer cells often carry repair defects and maintain high mutation frequencies.
PARP inhibitor
PARP inhibitors are anticancer drugs that block PARP enzymes involved in single-strand break repair. Tumors lacking BRCA genes also lack homologous recombination repair, so PARP inhibition causes lethal DNA damage—an example of synthetic lethality. Drugs such as olaparib are approved for clinical use. They exemplify precision medicine targeting DNA repair.
DNA damage response
The DNA damage response (DDR) is a signaling network that senses damage and coordinates cell-cycle arrest, repair or apoptosis. Kinases such as ATM, ATR and CHK1/2 act as central hubs. Proper DDR preserves the genome. Excess damage or DDR failure triggers cell death or tumorigenesis. DDR components are major targets in cancer therapy.