a holliday in science: robin holliday, ph.d., frs and faa (1932–2014)

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Please cite this article in press as: M.A. Resnick, A Holliday in science: Robin Holliday, Ph.D., FRS and FAA (1932–2014), DNA Repair (2014), http://dx.doi.org/10.1016/j.dnarep.2014.04.007 ARTICLE IN PRESS G Model DNAREP-1946; No. of Pages 1 DNA Repair xxx (2014) xxx–xxx Contents lists available at ScienceDirect DNA Repair j ourna l ho me pa ge: www.elsevier.com/locate/dnarepair A Holliday in science: Robin Holliday, Ph.D., FRS and FAA (1932–2014) Science today is just different. . .large projects, big data, sequenced genomes, expression arrays and high throughput this and that. Back then over 50 years ago, clean answers were hard to come by in the developing arena of molecular biology. But there were lots of genetic systems and data to drive ones appetite for figuring out how genomes change, how cells protect their valued chromosomes and beginning to understand evolutionary common- alities of DNA transactions. Robin Holliday was a man fit for the 60s, an iconoclast always critiquing and delighting in scientific controversy (or con-trah-fo-see, in Robin’s accent) and working outside-the-box. By 1969 at the age of 37 he was already head of the Genetics Division and solidly at the center of genetics with his Holliday model for recombination firmly ensconced in the thinking of most geneticists. Robin had been brought to the National Institute for Medi- cal Research, in Mill Hill, London, by Sir Peter Medawar who had received a Nobel Prize for work in immunology. The Institute was a powerful center for immunology, microbiology, biochemistry and chemistry. My mentor Bob Mortimer, one of the “fathers” of yeast genetics, brought my attention to Robin’s classic 1964 paper on recombination and gene conversion in Genetical Research, a lead- ing genetics journal at the time. Being the 60s, it was time for even more change and enlightenment, which led my wife, new- born child and me from Berkeley to London for an NIH postdoc fellowship and what I now view as my Holliday in science. At the age of 36, Robin’s physical presence was a bit of today’s Harry Pot- ter and everything that I hoped an English scientist would be like, including gold-rimmed glasses, a little on the short side, very, very clever in discussion and also a fine bowler in cricket (he kept telling me “don’t throw the bat,” a problem with all the American cricket novices). I was introduced to Ustilago maydis, an organism I always considered rather ugly compared to the smooth colonied budding yeast that was easy to mate, dissect and follow meiosis. None of that for Ustilago, which I am sure fit well with Robin’s challenging nature. But, he cleverly teased all sorts of genetics from this smut fungus that needed to be mated in corn where it also did its meiotic thing. He identified the first eukaryotic repair and recombination mutants and eventually, motivated through his collaborations with Geoff Banks and later Bill Holloman, some Robin Holliday passed away April 9, 2014. of the still profound understandings of the 3R mechanisms of DNA metabolism: replication, repair and recombination. Many of Robin’s contributions to the 3Rs and epigenetics are described in his 2004 and 2011 retrospective papers in this journal (DNA Repair v3, 671–682 and v10, 993–999, respectively). Robin was one of those broad thinkers whose first principles approach led him to make major contributions in the aging and the epigenetics as well as the 3R fields. He had this sixth sense of what cells could do with their DNA and was willing to make big com- mitments to get them to reveal their secrets. Importantly, I saw his enthusiasm and creativity infuse us all and extend into our tra- ditional 4:00 pm teatime and après-lab pub discussions. All ideas were welcomed, usually discarded, and occasionally even emerged later in experiments. Discussions often moved into politics and art, which is not surprising given Robin’s childhood years in exotic places, his exceptional talent as a sculptor and his culinary skills. Collaboration, not competition, was the norm as was exem- plified by Robin’s many collaborative papers. There was an expectation of openness and intellectual support within the lab and across the division. We were even beginning to proselytize gene conversion to our immunology colleagues at Mill Hill in discussions with Av Mitchison and Marty Raff. Robin’s Holliday model is more than DNA interactions generat- ing repair and diversity, the Holliday model is a way to approach science that many of us were fortunate to have experienced. We carried away the Holliday approach to thinking about science that remains with me to this date. (Personally, this approach led to my development of the initial model for repair of double strand breaks, which needless to say included a Holliday junction.) Looking back, those were golden years. The glow continues as evidenced by an upcoming international meeting whose central focus is the 50th anniversary of the Holliday model. Robin left us with several answers, but more importantly many challenges, for which we continue to be grateful. Michael A. Resnick Laboratory of Molecular Genetics, NIH-NIEHS, United States Available online xxx 1568-7864/$ see front matter http://dx.doi.org/10.1016/j.dnarep.2014.04.007

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Page 1: A Holliday in science: Robin Holliday, Ph.D., FRS and FAA (1932–2014)

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ARTICLE IN PRESSG ModelNAREP-1946; No. of Pages 1

DNA Repair xxx (2014) xxx–xxx

Contents lists available at ScienceDirect

DNA Repair

j ourna l ho me pa ge: www.elsev ier .com/ locate /dnarepai r

Holliday in science: Robin Holliday, Ph.D., FRS and FAA (1932–2014)�

Michael A. Resnick

Science today is just different. . .large projects, big data,equenced genomes, expression arrays and high throughput thisnd that. Back then over 50 years ago, clean answers were hard toome by in the developing arena of molecular biology. But thereere lots of genetic systems and data to drive ones appetite forguring out how genomes change, how cells protect their valuedhromosomes and beginning to understand evolutionary common-lities of DNA transactions. Robin Holliday was a man fit for the0s, an iconoclast always critiquing and delighting in scientificontroversy (or con-trah-fo-see, in Robin’s accent) and workingutside-the-box. By 1969 at the age of 37 he was already head ofhe Genetics Division and solidly at the center of genetics with hisolliday model for recombination firmly ensconced in the thinkingf most geneticists.

Robin had been brought to the National Institute for Medi-al Research, in Mill Hill, London, by Sir Peter Medawar who hadeceived a Nobel Prize for work in immunology. The Institute was aowerful center for immunology, microbiology, biochemistry andhemistry. My mentor Bob Mortimer, one of the “fathers” of yeastenetics, brought my attention to Robin’s classic 1964 paper onecombination and gene conversion in Genetical Research, a lead-ng genetics journal at the time. Being the 60s, it was time forven more change and enlightenment, which led my wife, new-orn child and me from Berkeley to London for an NIH postdocellowship and what I now view as my Holliday in science. At thege of 36, Robin’s physical presence was a bit of today’s Harry Pot-er and everything that I hoped an English scientist would be like,ncluding gold-rimmed glasses, a little on the short side, very, verylever in discussion and also a fine bowler in cricket (he kept tellinge “don’t throw the bat,” a problem with all the American cricket

ovices).I was introduced to Ustilago maydis, an organism I always

onsidered rather ugly compared to the smooth colonied buddingeast that was easy to mate, dissect and follow meiosis. None ofhat for Ustilago, which I am sure fit well with Robin’s challengingature. But, he cleverly teased all sorts of genetics from this

Please cite this article in press as: M.A. Resnick, A Holliday in scienc(2014), http://dx.doi.org/10.1016/j.dnarep.2014.04.007

mut fungus that needed to be mated in corn where it also didts meiotic thing. He identified the first eukaryotic repair andecombination mutants and eventually, motivated through hisollaborations with Geoff Banks and later Bill Holloman, some

� Robin Holliday passed away April 9, 2014.

568-7864/$ – see front matterttp://dx.doi.org/10.1016/j.dnarep.2014.04.007

of the still profound understandings of the 3R mechanisms ofDNA metabolism: replication, repair and recombination. Many ofRobin’s contributions to the 3Rs and epigenetics are described inhis 2004 and 2011 retrospective papers in this journal (DNA Repairv3, 671–682 and v10, 993–999, respectively).

Robin was one of those broad thinkers whose first principlesapproach led him to make major contributions in the aging and theepigenetics as well as the 3R fields. He had this sixth sense of whatcells could do with their DNA and was willing to make big com-mitments to get them to reveal their secrets. Importantly, I sawhis enthusiasm and creativity infuse us all and extend into our tra-ditional 4:00 pm teatime and après-lab pub discussions. All ideaswere welcomed, usually discarded, and occasionally even emergedlater in experiments. Discussions often moved into politics andart, which is not surprising given Robin’s childhood years in exoticplaces, his exceptional talent as a sculptor and his culinary skills.

Collaboration, not competition, was the norm as was exem-plified by Robin’s many collaborative papers. There was anexpectation of openness and intellectual support within the lab andacross the division. We were even beginning to proselytize geneconversion to our immunology colleagues at Mill Hill in discussionswith Av Mitchison and Marty Raff.

Robin’s Holliday model is more than DNA interactions generat-ing repair and diversity, the Holliday model is a way to approachscience that many of us were fortunate to have experienced. Wecarried away the Holliday approach to thinking about science thatremains with me to this date. (Personally, this approach led to mydevelopment of the initial model for repair of double strand breaks,which needless to say included a Holliday junction.)

Looking back, those were golden years. The glow continues asevidenced by an upcoming international meeting whose centralfocus is the 50th anniversary of the Holliday model. Robin left uswith several answers, but more importantly many challenges, forwhich we continue to be grateful.

e: Robin Holliday, Ph.D., FRS and FAA (1932–2014), DNA Repair

Laboratory of Molecular Genetics, NIH-NIEHS,United States

Available online xxx