The Work That Earned Aziz Sancar the Nobel Prize: Mechanistic DNA Repair
In this article
On 7 October 2015, the Royal Swedish Academy of Sciences announced that the year's Chemistry Nobel Prize would go to three scientists: Tomas Lindahl, Paul Modrich and Aziz Sancar. The reason was one sentence: "For mechanistic studies of DNA repair." This article explains what lay behind that sentence, precisely what Aziz Sancar discovered and how it translates into cancer treatment today.
DNA is not a stable molecule. As the Nobel Committee's presentation speech stated, spontaneous chemical processes create thousands of potentially devastating lesions in a cell's genome every day . Add ultraviolet rays, chemical carcinogens and copying errors during every cell division. We survive because cells continually repair this damage.
The award going to three people was no coincidence. Each resolved a different repair mechanism — they did not share one finding, but elucidated three complementary systems. Lindahl solved base excision repair, Modrich mismatch repair, and Sancar nucleotide excision repair . All three went beyond saying "repair exists" to show which protein does what, in which order at the molecular level. This is precisely what "mechanistic" means in the award citation.
| The prize | 2015 Nobel Prize in Chemistry |
|---|---|
| Official citation | "for mechanistic studies of DNA repair" — for mechanistic studies of DNA repair |
| Announcement | 7 October 2015 |
| Ceremony | 10 December 2015, Stockholm |
| Laureates | Tomas Lindahl (born 1938, Stockholm) · Paul Modrich (born 1946, Raton, New Mexico) · Aziz Sancar (born 8 September 1946, Savur, Mardin) |
| Institutions | Francis Crick Institute / Clare Hall (Lindahl) · Howard Hughes Medical Institute and Duke University (Modrich) · University of North Carolina, Chapel Hill (Sancar) |
| Prize amount | 8 million Swedish kronor, divided equally among three |
| Sancar's Nobel lecture | 8 December 2015 — "Mechanisms of DNA Repair by Photolyase and Excision Nuclease" |
Three Mechanisms, Three Different Problems
Not all DNA damage is alike. Spontaneous base deterioration, a wrong letter during copying and UV joining adjacent bases are three problems, solved by three separate cellular teams.
| Mechanism | What damage does it repair? | Who elucidated it? |
|---|---|---|
| Base excision repair base excision repair |
Spontaneous chemical deterioration of one base, such as cytosine becoming uracil | Tomas Lindahl 1974: uracil-DNA glycosylase enzyme |
| Mismatch repair mismatch repair |
Insertion of a wrong letter during copying | Paul Modrich 1989: methyl groups mark which strand is correct |
| Nucleotide excision repair nucleotide excision repair |
Bulky lesions distorting the helix — UV-induced thymine dimers, chemical carcinogen adducts, cisplatin adducts | Aziz Sancar 1983: dual incision by UvrA, UvrB and UvrC proteins |
One figure illustrates mismatch repair's effectiveness: the system reduces DNA copying error frequency by approximately a thousandfold — correcting, in the Nobel speech's words, %99,9 of errors. For inheritance's molecular foundation, read Mendel's pea experiments; for the technical history of reading and copying DNA, see our PCR article for more information.
What Exactly Did Sancar Discover?
He elucidated the cell's most versatile repair team. Nucleotide excision repair addresses not single-base chemical deterioration but bulky damage distorting the DNA helix : UV joining adjacent thymines into thymine dimers, chemical fragments added by tobacco-smoke carcinogens and, critically for cancer therapy, DNA adducts left by platinum chemotherapies such as cisplatin.
What Sancar did was reconstitute the system in bacteria. In 1982, he ran repair from start to finish in a test tube with purified proteins, publishing in 1983. The mechanism was:
Figure 1 · Nucleotide Excision Repair — Sancar's Mechanism
Steps derive from the bacterial system (UvrA, UvrB, UvrC); humans use the same principle with more proteins. Excision length differs between organisms, as noted below.
Why Work in Bacteria? This is a recurring Nobel biology story: understand a complex human system by finding its simplest form. Reducing repair to three bacterial proteins provided a map for the dozens involved in humans. The same strategy worked in the discovery of CRISPR-Cas9 — bacterial antiviral defense became a human genome editing tool.
From Savur to Stockholm: A Chronology
Sancar's route is among science's most unusual. Dates below come from his Nobel biography and official records.
One detail in this chronology is easily missed: When Sancar began the Nobel-winning work, he was a postdoctoral researcher who had moved into basic science in his thirties after two years of provincial medical practice in Türkiye. He counters the idea of a scientific career proceeding at the "right age, in the right order". The discovery was recognized thirty-two years later — a typical gap between basic-science discovery and award.
Maxicell: Correcting a Common Error
One often-repeated claim says: "Purifying DNA repair enzymes, he developed maxicell as a purification method ." This needs correction in two respects.
First: maxicell is not a purification method. In plasmid-carrying bacteria, it helps identify which proteins the plasmid encodes . The principle: recA and uvrA mutant cells, unable to repair DNA, of E. coli are exposed to UV. Their chromosome fragments, while the smaller, less damaged plasmid DNA survives and multiplies. Labeled amino acids are then supplied; only plasmid proteins can be produced and are labeled. Thus, the method does not separate proteins, but identifies proteins.
Second: no source supports the claim "still used by many researchers". What can be verified is Sancar's statement in his Nobel biography that the maxicell paper is his most cited career publication (Sancar A, Hack AM, Rupp WD, Journal of Bacteriology, 1979).
A third detail: this work was not done in doctoral supervisor Claud Rupert's Dallas laboratory, but at Yale with W. Dean Rupp . Rupert belongs to the photolyase period, Rupp to excision repair.
This matters: after cloning uvrA, uvrB and uvrC, Sancar needed to identify their proteins. Maxicell made this possible, after which proteins could be purified and combined in a tube. Understanding why he developed it explains how the discovery became possible. The method enabled the discovery; it was not the discovery itself.
Photolyase: Sancar's First Love, an Enzyme We Lack
His scientific story begins with another enzyme. In 1958, Claud Rupert discovered photolyase , an enzyme with an extraordinary capability: it binds to a thymine dimer produced by ultraviolet light and uses blue light energy to undo them in place. No cutting, removal or rewriting — reversal in one step. Sancar cloned its gene in 1975.
Eighteen years later, his team showed that humans lack photolyase.
Figure 2 · Two Ways to Repair UV Damage — and Which Humans Lack
Sancar's team's 1993 study E. colieasily detected photolyase in yeast and rattlesnake extracts but not human cells. The method could detect even 10 molecules per cell.
Another example of scientific integrity: Sancar conducted the study showing his career-defining enzyme absent in humans in his own laboratory and published it. Its human relevance emerged elsewhere: relatives in this enzyme family set mammalian biological clocks as cryptochromes . This became his second major research line and linked directly to chemotherapy timing, discussed in our circadian rhythm and chemotherapy article previously.
What Happens When Repair Fails? Two Diseases, Two Lessons
The clearest way to understand repair's importance is to examine congenital defects. Two diseases illustrate two different systems.
Xeroderma Pigmentosum — Failure of Sancar's Pathway
Xeroderma pigmentosum involves nucleotide excision repair being genetically defective. The mechanism in Figure 1 fails, with consequences demonstrating its vital importance.
| In xeroderma pigmentosum | Compared with the general population | Age of onset |
|---|---|---|
| Nonmelanoma skin cancer (basal and squamous cell) | More than 10.000-fold risk | Median age 9 — approximately 60 years earlier |
| Melanoma | More than 2.000-fold risk | Median age 22 — over 30 years earlier |
| Internal organ tumors | 34-fold risk | Approximately 50 years earlier |
Median lifespan with neurological involvement is 29 years, without it, 37 years. These figures show that solar UV damage occurs every day and a system repairs it daily. When it fails, cancer normally appearing over sixty years develops at nine. For melanoma symptoms and stages, see our separate article for details.
Lynch Syndrome — Failure of Modrich's Pathway
An inherited defect in a mismatch repair gene (MLH1, MSH2, MSH6, PMS2 or EPCAM) means Lynch syndrome , the most common cause of hereditary colorectal cancer.
| Gene | Colorectal cancer risk by age 70 | Endometrial cancer risk by age 70 |
|---|---|---|
| MLH1 | %46 (men) / %44 (women) | %35 |
| MSH2 | %46 (men) / %42 (women) | %46 |
| MSH6 | %12 (men) / %20 (women) | %41 |
| PMS2 | %3 | %12–13 |
| EPCAM | %75 | %12 |
Two points matter when reading this table. First, these rates are calculated "by age 70", not "over a lifetime" ; these are different. Second, and clinically most useful, risk varies greatly by gene. With MLH1 or MSH2, median colorectal cancer onset is age 44 , while for PMS2 it is 61–66 with much lower risk. Lynch is not one uniform condition; the gene changes surveillance frequency and preventive surgery decisions. Colonoscopy intervals are discussed in our separate article, and preventive surgery for inherited risk in our BRCA article previously.
Both diseases teach the same lesson: cancer often arises not "because DNA was damaged", but because the damage could not be repaired . Damage is already continuous — mutations are inevitable. The balance between damage and repair determines cancer. This balance is detailed in our article on how DNA damage affects cancer development as a fuller explanation.
The Central Paradox: Preserve Repair and Block It
Understanding repair raises an inevitable question. Cancer cells use it even more than healthy cells, continually clearing rapid-division damage. A repair-blocking drug might kill tumors, but it would also inhibit healthy-cell repair.
This classic pharmacological problem is called the therapeutic window: the range harming tumors without harming patients. For repair pathways, it is very narrow. How was this paradox overcome?
Through an idea called "synthetic lethality". Losing either of two genes alone allows survival, but losing both kills the cell. If a tumor cell already has one defect, blocking the other kills only that cell; healthy cells tolerate treatment because both pathways remain intact. Drug selectivity therefore comes from the tumor's pre-existing defect as its basis.
Figure 3 · Synthetic Lethality: Why Do PARP Inhibitors Kill Only Certain Tumors?
PARP repairs single-strand breaks. BRCA genes participate in homologous recombination repairing double-strand breaks. The diagram shows four combinations.
This clearly shows Nobel-winning basic science reaching the clinic. Without the mapped pathways, we would not know which tumor lacks which repair mechanism or which drug suits whom. This produced one of today's clearest examples of personalized treatment.
What Is Available Clinically Today? Concrete Applications
"Basic science will help someday" often sounds abstract. Here it is concrete. All the following arose from repair pathway mapping and are currently licensed treatments.
1. Immunotherapy for Repair-Defective Tumors
Mismatch repair-deficient (dMMR) or high microsatellite instability (MSI-H) tumors accumulate many mutations from unrepaired errors. These produce foreign protein fragments, making tumors visible to immunity.
23 May 2017 marks a turning point in cancer drug history. The FDA approved pembrolizumab regardless of the organ of origin, requiring only MSI-H/dMMR status. In the FDA's words, "this is the FDA's first tissue/site-agnostic approval." For the first time, a cancer drug was approved not according to its type but molecular defect . Approval relied on 5 single-arm studies with 149 patients : the response rate was %39,6, and in %78 of responders response lasted at least 6 months. Accelerated approval became full approval on 28 March 2023 as the regulatory transition.
The most striking example involved locally advanced, mismatch repair-defective rectal cancer treated, instead of surgery, radiotherapy or chemotherapy, only with dostarlimab (for 6 months, every 3 weeks). At reporting, evaluable patients showed clinical complete response in 14 of 14 patients ; none required chemotherapy, radiation or surgery, and no grade 3–4 adverse effects occurred.
This is exciting but should not be exaggerated — our caution. The evaluated sample was 14and median follow-up at reporting was 6,8 months. Rectal recurrence can take years. The approach also applies only to dMMR tumors of this type; most rectal cancers are outside this group. Headlines about nonsurgical rectal treatment often omit both conditions. Our colorectal cancer article provides the overall treatment framework.
2. Drugs Targeting Repair Defects: PARP Inhibitors
The clinical application of synthetic lethality in Figure 3 is PARP inhibition. The first United States approval in this class went to olaparib on 19 December 2014 through accelerated approval for patients with inherited BRCA mutations after three or more chemotherapy lines and advanced ovarian cancer as the indication.
Within ten years, this indication expanded across cancers. Current olaparib indications include advanced ovarian cancer (first-line and recurrent maintenance), HRD-positive disease with bevacizumab, BRCA-mutated HER2-negative breast cancer (early and metastatic), BRCA-mutated metastatic pancreatic cancer maintenance and BRCA/HRR-mutated metastatic castration-resistant prostate cancer among approved indications.
The strongest evidence came from early breast cancer's OlympiA study. High-risk early breast cancer patients with inherited BRCA mutations, totaling 1.836 patients, received one year of olaparib or placebo after standard treatment:
| OlympiA — 3-year results | Olaparib | Placebo |
|---|---|---|
| Invasive disease-free survival | %86,1 | %77,3 |
| Distant disease-free survival | %88,0 | %81,0 |
| Overall survival | %92,0 | %89,1 |
Overall survival difference 3,8 points, hazard ratio 0,68 (p=0,009). Relative and absolute differences must be read together: %32 relative risk reductionover three years corresponds to 3,8 points of absolute benefit . Both are true; the chosen measure affects the news tone. On this basis, the FDA approved olaparib on 11 March 2022 as adjuvant treatment for high-risk early BRCA-mutated breast cancer.
3. The Realistic Side
The therapeutic window problem is not solved on paper. Olaparib's product information warns of myelodysplastic syndrome and acute myeloid leukemia , with pooled incidence of %1,2 (among 2.219 patients, 26 cases) and among these 26 cases, %54 were fatal. Average onset followed approximately two years of treatment. A major confounder: all had previously received platinum or other DNA-damaging treatments, so the PARP-attributable share is unclear. Indeed, a meta-analysis of 23 randomized studies and 8.857 patients found secondary cancer rates of %0,9 versus %0,7 , with a difference that was not statistically significant. Both findings are true and should be reported together.
New repair-targeting drug classes face the same issue. WEE1 inhibitor adavosertibin a phase 2 recurrent uterine serous carcinoma trial showed a %26 response rate — it worked. But %60,6 had grade 3 or higher side effects and development was discontinued. Other candidates such as ATR inhibitor ceralasertib remain in clinical development; when this article was prepared, no FDA-approved drug targeting ATR, ATM, WEE1 or DNA-PK was found.
In summary: targeting DNA repair works, but only when we know which repair pathway is defective. Blind targeting encounters toxicity, as with adavosertib. This returns to Nobel's core lesson: drug design requires mechanistic understanding.
A Second Line: Does Repair Have a Clock?
Photolyase research led somewhere unexpected. Mammalian relatives in its family, cryptochromes , do not sense light and repair DNA; instead they set the biological clock . Sancar's laboratory asked: if clock and repair proteins are related, might repair itself vary during the day?
Yes. One reported finding: mice exposed to UVB in the morning were, compared with those receiving the same dose in the evening , more likely to develop invasive skin cancer by approximately fourfold . The team also mapped platinum adduct repair in cisplatin-treated mice every four hours over one day, genome-wide at single-nucleotide resolution.
Two serious barriers to human extrapolation are often missed — our warning. First, findings were obtained in mice . Second, and more importantly, mice are nocturnal: their "morning" is not biologically our morning. Direct advice such as "sunbathe in the evening" or "take chemotherapy at this hour" cannot be drawn. The underlying idea of time-varying repair is sound and deserves human testing, but practical advice is premature. We discuss this in our chemotherapy timing article in detail.
The same caution applies to other Sancar-related news. A study was presented in Türkiye as a "discovery to make people stop smoking"; we examined its actual meaning in a separate article . Affection for a scientist is good, but exaggerated findings ultimately harm that scientist most.
XR-seq: Mapping Repair
Developed by Sancar in 2015, XR-seq represents the transition from mechanism to map. Its elegant idea: human repair releases a fragment approximately 30 nucleotides long . Collecting and sequencing these reveals which genomic site is repaired, when and how intensely at single-nucleotide resolution.
A year later, application to cisplatin showed damage distributed almost uniformly, but repair very unevenly — varying with transcription and chromatin structure. Mutation burden depends less on damage received than how well it is repaired. Why mutation location matters is discussed in in a separate article our previous article.
DROZDOGAN Academy Commentary
In Türkiye, Aziz Sancar's story is mostly told as a story of national pride . Its real value lies elsewhere: a physician moved from two years of provincial practice into basic science in his thirties, reconstituting a mechanism that would earn recognition thirty years later in a test tube. This is not a nationality story but a story of method.
⚡ Why it matters
Much of today's personalized oncology emerges from these three scientists' pathways: immunotherapy for MSI-H tumors, PARP inhibitors for BRCA mutations and early screening in Lynch syndrome. None would be possible without knowing the proteins and mechanisms of repair. The seventh section provides a concrete answer to the value of basic science.
✅ Strengths
Sancar performed biology's hardest task: taking a process apart and rebuilding it. Reconstituting a mechanism with purified proteins proves genuine understanding, rather than speculation. Dual incision was also unexpected, hence the enzyme's name, "excinuclease" as a reflection of that discovery.
⚠️ Points requiring care
Three common errors recur. First, "Sancar discovered DNA repair": repair was known since the 1950s; he elucidated one mechanism and the award for three mechanisms went to three people . Second, maxicell described as protein purification: it identifies proteins, rather than purifies. Third, direct human lifestyle advice from mouse circadian data. All three should be corrected; these are our assessments.
🩺 Practical Meaning for Patients
Three concrete points. (1) With early colorectal or uterine cancer in the family, Lynch syndrome should be investigated; carriers' surveillance frequency and starting age differ. (2) If diagnosed with breast, ovarian, pancreatic or prostate cancer, ask whether BRCA and repair gene testing has been considered — results may change PARP options. (3) For bowel or uterine cancer, ask whether MSI/dMMR testing was performed; this result alone may open immunotherapy options. All three tests are available in Türkiye today.
❓ Open Question
The main bottleneck in repair-targeting drugs is not the target, but the therapeutic window. Adavosertib showed this clearly: it hit the tumor but also the patient. Widening the window probably requires better patient selection rather than stronger drugs, measuring the tumor's missing repair pathway beforehand. XR-seq is an early example; whether it enters clinical use remains a future question.
Conclusion: The 2015 Chemistry Nobel is among cancer biology's most practical awards. Its findings date to the 1970s and 1980s, reaching the clinic in 2014–2017. This delay reflects basic science's nature, not a flaw. National science policy is measured by willingness to accept that forty-year distance.
Frequently Asked Questions
- What Exactly Did Aziz Sancar Win the Nobel Prize For?
- The official citation is shared by three scientists: "For mechanistic studies of DNA repair." Sancar's contribution was nucleotide excision repair: bulky UV and chemical carcinogen damage removed by UvrA, UvrB and UvrC through cutting on both sides simultaneously . He reconstituted it in a tube in 1982 and published in 1983.
- Did He Win Alone?
- No. The prize was divided among Tomas Lindahl, Paul Modrich and Aziz Sancar as the three recipients, equally into three shares . Each elucidated a different mechanism: Lindahl base excision, Modrich mismatch, Sancar nucleotide excision repair.
- Did Sancar Discover DNA Repair?
- No. Cellular DNA repair was known since the middle of the 20. century. His contribution showed which proteins act, in what order and how at molecular detail. "Mechanistic" in the citation marks precisely this distinction.
- What Is Maxicell? A Protein Purification Method?
- No, it is not purification. Maxicell is a bacterial labeling method to identify which proteins the plasmid encodes identify proteins. Repair-defective bacteria receive UV; the chromosome fragments while plasmids survive, so only plasmid proteins are labeled. In his words, it is his most cited paper (1979).
- Do Humans Have an Enzyme Repairing Sun Damage with Light?
- No. Photolyase occurs in bacteria, yeast and many animals, but not humans. Interestingly, Sancar's own team, whose career began with the enzyme, demonstrated this (1993). Our only option is slower, more complex excision repair.
- Does Every Person with Defective Repair Get Cancer?
- No, but risk rises markedly. In xeroderma pigmentosum, nonmelanoma skin cancer risk compared with the general population is More than 10.000-fold, while Lynch colorectal cancer risk by age 70 varies by gene between %3 and %75 . A defect means substantially higher and earlier risk rather than certain cancer.
- Can Everyone Receive PARP Inhibitors?
- No. These work when a tumor already has a repair defect — typically BRCA mutation or a similar homologous recombination deficiency. Without it, selective effects are impossible, so genetic testing is required first.
- What Practical Benefits Do These Discoveries Have?
- Three points: with early familial colorectal or uterine cancer, investigation for Lynch syndrome; in breast, ovarian, pancreatic and prostate cancer, BRCA testing; in colorectal and uterine cancer, MSI/dMMR testing. All three can directly change treatment options.
Glossary
- DNA repair
- The enzyme systems detecting and correcting DNA damage. Different damage types require different systems.
- Nucleotide excision repair (NER)
- Removes bulky helix-distorting lesions by cutting on both sides. Sancar's mechanism.
- Base excision repair (BER)
- Repairs chemical deterioration of individual bases. Lindahl's mechanism.
- Mismatch repair (MMR)
- Corrects wrongly copied DNA letters. Modrich's mechanism, reducing error frequency approximately a thousandfold.
- Thymine dimer
- UV-induced joining of two adjacent thymine bases, distorting the DNA helix.
- Photolyase
- An enzyme using blue light energy to reverse thymine dimers in one step. Absent in humans.
- Cryptochrome
- A photolyase-family protein that sets mammalian biological clocks without repairing DNA.
- Excinuclease
- An enzyme complex cutting on both sides of damage, named for Sancar's dual-incision discovery.
- XR-seq
- A method collecting and sequencing excised fragments to map repair location and intensity genome-wide.
- Xeroderma pigmentosum
- An inherited nucleotide excision repair defect causing skin cancers at very young ages.
- Lynch syndrome
- An inherited mismatch repair gene defect, the most common cause of hereditary colorectal cancer.
- MSI-H / dMMR
- Tumor features indicating failed mismatch repair. Immunotherapy responses are markedly higher in such tumors.
- Synthetic lethality
- Loss of either gene alone is nonlethal, but combined loss kills the cell. The principle behind PARP inhibitors.
- PARP inhibitor
- Drugs blocking single-strand break repair, selectively affecting homologous recombination-deficient tumors.
- Therapeutic window
- The dose range harming tumors with acceptable patient harm. Narrow in DNA repair-targeted drugs.
Transparency note.
Verified: Official prize citation ("for mechanistic studies of DNA repair"), announcement on 7 October 2015 and ceremony on 10 December 2015, equal division of 8 million Swedish kronor, laureates' birth dates/places and institutions, and Sancar's lecture title from 8 December 2015 — from Nobel press releases, introductory pages, presentation speech and laureate pages. Mechanisms and dates (Lindahl 1974 uracil-DNA glycosylase; Modrich 1989 methyl-directed system; Sancar 1983, uvrA/uvrB/uvrC). Mismatch repair's "approximately thousandfold" error reduction and the speech's "%99,9". Bacterial excision length of 12–13 nucleotides from Nobel information and the Royal Swedish Academy poster. Human excision length of 24–32 nucleotides ("nominal 30-mer") from the Sancar laboratory and XR-seq paper. Biography (birth 8 September 1946 Savur; Istanbul Medicine entry November 1963 and top graduation 1969; medical practice 1969–1971 in Savur and Sürgücü; Claud Rupert's Dallas laboratory in 1973; photolyase cloning; July 1977 thesis defense; September 1977 Yale with W. Dean Rupp; 1979 maxicell paper; 1982–83 excinuclease; 1983 Chapel Hill move; Sarah Graham Kenan Professorship since 1997) from Nobel biography and UNC. Maxicell citation and abstract (J Bacteriol 1979;137(1):692–693). Human photolyase absence study (PNAS 1993;90:4389), with sensitivity of 10 molecules per cell. XR-seq citation (Genes & Development 2015;29:948) and cisplatin mapping (PNAS 2016;113:11507). All xeroderma and Lynch figures from NCBI GeneReviews. Pembrolizumab accelerated approval on 23 May 2017, FDA's "first tissue/site-agnostic approval", 149 patients, %39,6 response, in %78 of responders duration ≥6 months and full approval on 28 March 2023 (fda.gov and cancer.gov). Dostarlimab data (18 enrolled, 14 evaluable with %100 clinical complete response, 500 mg/3 weeks, 6 months, median follow-up 6,8 months, no grade 3–4 events). Olaparib accelerated approval on 19 December 2014 and indication (FDA letter), current indications (2025 information), 11 March 2022 early breast approval, OlympiA (1.836 patients; 3-year iDFS %86,1 versus %77,3; distant disease-free survival %88,0 versus %81,0; overall survival %92,0 versus %89,1, HR 0,68, p=0,009). MDS/AML warning (%1,2; 2.219 patients, 26 cases; %54 fatal) and 23 randomized studies / 8.857-patient meta-analysis of secondary cancers (%0,9 versus %0,7; nonsignificant). ADAGIO adavosertib (%26 response, %60,6 grade ≥3, development discontinued) and ceralasertib in clinical development.
Unverified: For photolyase cloning year, two official Nobel sources give different dates — Sancar's biography gives 1975, the introductory page 1976. We used his firsthand account and noted the difference. The Committee states only "thousands" of daily lesions; circulating exact claims such as "tens of thousands" were unverified and omitted. No official page directly stated olaparib was "the first approved drug in its class"; we stated only that approval on 19 December 2014 was the class's first, without a "first drug" claim. ERCC1's status as a validated clinical platinum-resistance biomarker could not be verified; therefore, no ERCC1 claim appears. No exact Nobel Foundation statement that Sancar was "Türkiye's first science Nobel" was found (Orhan Pamuk's 2006 Literature Prize was confirmed), so no such "first" wording was used. The Committee's detailed scientific background document was inaccessible.
Ownership of critiques: Our assessments include maxicell not being purification, unsupported current widespread use, work occurring in Rupp's rather than Rupert's laboratory, mouse circadian data not directly applying to humans including nocturnality, caution on dostarlimab sample and follow-up, reporting relative and absolute OlympiA differences together, and the error of saying Sancar discovered DNA repair. These assessments are our own. The three mechanisms, their discoverers and all numerical data belong to their sources.
Diagrams derive from verified statements; they contain no new data. Figure 3 is idealized logic, not real clinical safety, as stated beneath it.
References
- The Nobel Prize in Chemistry 2015 — press release, introductory text, presentation speech and laureate pages. NobelPrize.org, Royal Swedish Academy of Sciences.
- Sancar A. Nobel biography and lecture: "Mechanisms of DNA Repair by Photolyase and Excision Nuclease", 8 December 2015.
- Sancar A, Hack AM, Rupp WD. "Simple method for identification of plasmid-coded proteins." Journal of Bacteriology. 1979;137(1):692–693.
- Li YF, Kim ST, Sancar A. "Evidence for lack of DNA photoreactivating enzyme in humans." PNAS. 1993;90(10):4389–4393.
- Hu J, Adar S, Selby CP, Lieb JD, Sancar A. "Genome-wide analysis of human global and transcription-coupled excision repair of UV damage at single-nucleotide resolution." Genes & Development. 2015;29(9):948–960.
- "Cisplatin DNA damage and repair maps of the human genome at single-nucleotide resolution." PNAS. 2016;113(41):11507.
- GeneReviews (NCBI Bookshelf): Xeroderma Pigmentosum; Lynch Syndrome.
- U.S. Food and Drug Administration. "FDA grants accelerated approval to pembrolizumab for first tissue/site agnostic indication", 23 May 2017; and National Cancer Institute, Cancer Currents, updates in 2017 and 2023.
- U.S. Food and Drug Administration. Olaparib (Lynparza) approval letter, NDA 206162, 19 December 2014; current information (2025); "FDA approves olaparib for adjuvant treatment of high-risk early breast cancer", 11 March 2022.
- OlympiA results and PARP inhibitor secondary cancer meta-analysis — The ASCO Post.
- ADAGIO (adavosertib) — The ASCO Post, 2025; ceralasertib — NCI DCTD agent information.
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