Picking up the pieces - Tsuneko Okazaki
I first learned about Okazaki fragments in my undergraduate biochemistry class, when we learned how the DNA in every cell is copied so that it can divide.
DNA is a double helix – a twisted ladder. Each of the two side struts runs in an opposite direction, up and down (or ‘5 prime to 3 prime and 3 prime to 5 prime’ as biologists say), according to the directional stacking of the DNA letters, or bases, that make up the molecule. If it helps, imagine two long chains of stacked pint glasses laid side by side, one stack all facing in one direction and the other running the opposite way.
When DNA is copied, these two strands are pulled apart and complementary strands synthesised to match. For presumably boring reasons to do with evolution of protein structures, DNA polymerase, the enzyme that copies DNA, can only run in one direction. So the two sides of the ladder have to be copied in different ways. For one side this is no problem - the polymerase can just run along and make new DNA in an unbroken chain.
But the other side has to do some molecular gymnastics, twisting around in a loop so it can be fed into the polymerase machinery from the right direction, then popping out, twisting again and feeding in a new stretch, a bit further along. This creates short stretches of newly-copied DNA – Okazaki fragments - with gaps in between, that have to be patched up in order to create a perfect new helix.
(Oh, and if all of this sounds completely baffling, then check out this handy animation)
So, who was Okazaki? I always assumed that he was another of those guys from the classic era of molecular biology in the 1960s. Well, I was not only wrong, but I was also suffering from internalised patriarchy. It turns out there isn’t just one Okazaki – there’s two: Tsuneko and her husband Reiji.
Born Tsuneko Hara in 1933, in Nagoya, Japan, she was one of the first generation of Japanese women to take advantage of the country’s new post-war constitution, which allowed women to attend university alongside men. So Tsuneko went to the local university to study biology, graduating with a PhD and a husband-to-be in 1956. The Okazakis got married later that year and decided to set up a lab as well as a home together, still at Nagoya University.
It was a good move on Tsuneko’s part: at the time, it was very difficult for women to find jobs in science, apart from teaching, or even be recognised as researchers in their own right. But as long as Reiji had a position, she did too. Money was tight in post-war Japan. The roof of their lab leaked, and they often had to buy supplies out of their own pockets. Besides research, their main hobby was heading out to the local noodle shop to watch Sumo wrestling on TV, as they had no set of their own.
They decided to focus their collective scientific power on unravelling the mystery of DNA copying, or replication, investigating the intricate details of the process in frog and sea urchin eggs, moving between the US and Japan over the years.
Their key discovery came in the late 1960s. At the time it was known that DNA polymerase could copy DNA, and that it only went one way up the double helix, copying the so-called leading strand. But nobody could figure out how the opposite strand, known as the lagging strand, got copied.
After carrying out painstaking experiments with bacteria, the Okazakis realised that as well as making long, unbroken leading strands, DNA polymerase was also churning out much shorter pieces – the eponymous fragments. Of course, the Japanese couple were far too polite to name their discovery after themselves – the name ‘Okazaki pieces’ was bestowed by American biochemist Rollin Hotchkiss at a scientific conference in 1968, the year they published their findings.
Sadly, Reiji died of leukaemia in 1975, aged just 44. He was born in Hiroshima and was heavily exposed to radiation from the blast of the atomic bomb detonated over the town by the United States at the end of the Second World War.
Tsuneko kept going, running the lab by herself and making further important discoveries about DNA replication. While many of the men working in the field received Nobel prizes for their work in molecular biology through that golden age of the 60s and 70s – and many said that Reiji would have been a worthy laureate, had he lived - somehow Tsuneko alone never got the nod.
Yet she was an equal partner in the research, and after Reiji’s death it was Tsuneko who repeated the complex biochemical experiments time after time to prove that their fragments were real and this was how DNA replication worked.
Perhaps the problem was that Reiji was able to dedicate himself to his work in a manner that Tsuneko herself described as "typical old-fashioned Japanese male - he wouldn't even boil a kettle and would just drink water when alone".
It’s perhaps this attitude, which was highly pervasive in Japanese society, that contributed to his wife being seen as playing a supporting part rather than an equal role. It was always Reiji who was invited to speak at conferences, and when he was awarded the prestigious Asahi Prize, Tsuneko was invited to the award ceremony as his spouse, not as his co-researcher.
Tsuneko also had to take on the responsibilities of raising their two children as well as the scientific ‘housework’ involved in running the lab.
Struggling with finding childcare in 1970s Japan, she devoted a lot of her energy to campaigning for better support for working mothers – something that another woman who did manage to win a Nobel, fruit fly biologist Janni Nusslein-Volhard has addressed by setting up a foundation in her native Germany to support women scientists with children.
Still alive today, Tsuneko Okazaki is now seen as a highly respected as a molecular biologist and one of Japan’s leading scientific minds. She prefers to focus on her work, rather than the male-centred scientific culture that meant she was all too often seen as just ‘the wife’, saying "That sort of thing happened a lot, but it's trivial. What's important in research is how you find a good problem to tackle, and solve it."
References and further reading:
Mechanism of DNA chain growth. I. Possible discontinuity and unusual secondary structure of newly synthesized chains. Okazaki R, Okazaki T, Sakabe K, Sugimoto K, Sugino Proc Natl Acad Sci U S A. 1968 Feb;59(2):598-605