Nicholas R. Cozzarelli dies

Nicholas R. Cozzarelli, who made fundamental discoveries about how gyrases and topoisomerases untangle DNA, and revolutionized the Proceedings of the National Academy of Sciences (PNAS) as the journal's editor-in chief, died last month of complications of treatment for Burkitt's lymphoma. He was 67."He basically was a pioneer in thinking about all the ways that, as he put it at the end of his life, protein machines bully and push DNA around," Michael Botchan of the University of California at Berkeley, a colleague and friend, explained. "His insights into the physical functional structural state of DNA were a major contribution," Arthur Kornberg at Stanford University Medical School told The Scientist.Cozzarelli became interested in gyrases as a postdoc in Kornberg's lab, where he mapped drug resistance to quinolones to one of the subunits of gyrase. The discovery, which he once called his proudest achievement as a scientist, brought quinolones to the forefront of clinical medicine and paved the way for the use of topoisomerase inhibitors like cisplatin in chemotherapy, Botchan noted.After Stanford, Cozzarelli moved to the University of Chicago in 1968, and then to Berkeley in 1982. He continued to study the uncoiling of DNA, demonstrating that the molecule un-knotted itself by passing a segment through an enzyme-bridged transient double break. The mechanism by which DNA managed to replicate itself had puzzled scientists since Watson and Crick first described the molecule's structure in 1953, Botchan noted.Cozzarelli became editor in chief at PNAS in 1995. He took the job, his Berkeley colleague Carlos Bustamante told The Scientist, because he felt that the journal had great unrealized potential as a scientific publication. At that time, PNAS only accepted submissions through members of the Academy. He created a second track to allow scientists to submit manuscripts directly -- which Diane Sullenberger, PNAS' executive editor since 1996, called his "single most striking accomplishment" during his time at the journal."Nick believed in a level playing field," she explained in an Email. "Now 84% of our submissions and almost half of our published papers are submitted directly" via this more-recent system.Cozzarelli also expanded the editorial board from 26 to more than 140, and boosted publication of papers in the non-biological sciences. "He totally changed the structure and created a very active, dynamic editorial board," Solomon H. Snyder, director of neuroscience at Johns Hopkins and senior editor at PNAS, told The Scientist. Snyder added that Cozzarelli was the right person for the tough job of telling academy members their papers might not be up to snuff. "He could do it in such an open, friendly, and honest way that no one was ever mad at him."Cozzarelli was able to maintain his pioneering work in science while editing the journal by choosing his scientific and editorial collaborators wisely, colleagues agree. "He also cared deeply about his family, friends, and culture," Sullenberger said. "He found time to travel and thoroughly enjoy life. He was one of the few who could strike the right balance."Cozzarelli grew up in Jersey City, New Jersey, the son of immigrants from southern Italy. He attended Princeton on a full scholarship, graduating in 1960. After a year at Yale Medical School he transferred to Harvard Medical School, graduating with a PhD in biochemistry in 1966.In his work as an editor, mentor, and teacher, Cozzarelli liked to challenge people, his colleagues say. "A lot of people thought he was kind of rough and tough, but it was really out of love for science and people that he challenged and pushed them," Botchan recalled.Cozzarelli is survived by his wife, Linda, a daughter, Linda Cozzarelli-Wood, and his brothers Francis and Angelo.Anne Harding aharding@the-scientist.comThe Cozzarelli Lab Home Page https://mcb.berkeley.edu/labs/cozzarelli/In Memoriam: PNAS Editor-in-Chief Nicholas R. Cozzarelli (1938-2006) https://www.pnas.org/cgi/content/abstract/0602531103v1Michael Botchan https://mcb.berkeley.edu/faculty/BMB/botchanm.htmlH. Black, "Agricultural antibiotics scrutinized," The Scientist, June 12, 2000. https://www.the-scientist.com/article/display/11896/Ask a Scientist: Nicholas Cozzarelli https://mcb.berkeley.edu/faculty/BMB/botchanm.htmlP. O. Brown and N. R. Cozzarelli,"A sign inversion mechanism for enzymatic supercoiling of DNA," Science, November 30, 1979. PM_ID 227059Carlos Bustamante https://alice.berkeley.edu/main/carlos.htmlSolomon H. Snyder https://www.mbg.jhmi.edu/FacultyDetails.asp?PersonID=726

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