Lindahl, Tomas

Tomas Lindahl, (born January 28, 1938, Stockholm, Sweden), Swedish biochemist known for his discovery of base excision repair, a major mechanism of DNA repair, by which cells maintain their genetic integrity. Base excision repair corrects damage sustained by individual DNA bases (adenine, cytosine, guanine, and thymine), which frequently occurs as a result of spontaneous DNA decay, a process suspected of contributing to aging, mutation, and the development of cancer. For his discoveries, Lindahl received the 2015 Nobel Prize for Chemistry (shared with American biochemist Paul Modrich and Turkish-American biochemist Aziz Sancar).

Lindahl graduated with a Ph.D. from the Karolinska Institute in Stockholm, Sweden, in 1967, and three years later he completed an M.D. there. In 1969, following postdoctoral studies in the United States, he joined the faculty at the Karolinska Institute. He remained at the institute until 1978, when he went to the University of Gothenburg, where he served as a professor of medical and physiological chemistry. In the early 1980s he left Gothenburg to take a position as principal scientist at the Imperial Cancer Research Fund (later Cancer Research UK) in London, where from 1984 to the early 2000s he directed the organization’s Clare Hall Laboratories (later part of the Francis Crick Institute).

Lindahl’s early research focused initially on two topics, the Epstein-Barr virus (EBV) and spontaneous DNA damage that originated endogenously (within cells). In his work on EBV, he and his colleagues discovered that the virus’s genome exists in different states in transformed cells, typically being present either as nonintegrated circular DNA or as fragments integrated into the host genome. Although Lindahl was intrigued by the findings, he was more impressed by the phenomenon of endogenous DNA damage, which introduces thousands of potentially mutagenic lesions into a single mammalian genome each day. By the late 1970s he had begun to identify key components of the base excision repair pathway, specifically enzymes known as DNA glycosylase and apurinic/apyrimidinic (AP) endonuclease.

Over the course of the next three decades, Lindahl and his colleagues discovered multiple DNA excision repair enzymes, in both bacterial and mammalian cells. He and his coworkers further deduced the steps of base excision repair, whereby DNA glycosylase identifies and removes the damaged base from the DNA strand, AP endonuclease makes an incision at the affected site, lyase or phosphodiesterase enzymes clear the site of remaining fragments of sugar-phosphate groups (components of the DNA backbone), DNA polymerase fills the gap in the strand with one or more nucleotides (bases linked to sugar and phosphate groups), and the incision is sealed. Lindahl continued to investigate DNA-repair mechanisms late into his career. His findings ultimately proved critical to furthering scientists’ understanding of the role of mutagenesis in disease, particularly cancer, where the mutation and consequent dysfunction of DNA-repair proteins facilitates the process of malignant transformation.

Lindahl retired to the title of emeritus director of the Clare Hall Laboratories, where he closed his laboratory in 2009. Under his leadership, Clare Hall developed a reputation as a highly productive centre for research on DNA repair, DNA replication, and cell division. In addition to the Nobel Prize, Lindahl was recognized for his work with multiple other awards, including the 2007 Royal Medal and the 2010 Copley Medal of the Royal Society. He was an elected fellow of the Royal Society (from 1988) and an elected member of the Royal Swedish Academy of Sciences.