Dr. Nitika Taneja has dedicated over a decade to studying chromatin: a way of packaging our DNA by small proteins called histones. Only five years after starting her own lab, Taneja already knows how to shake up the field considerably. The current consensus in science is: the function of a type of chromatin called heterochromatin is to tightly pack genes and thus silence them. In Nature Cell Biology, Taneja and her team now present a series of experiments that turn this idea about heterochromatin on its head.
The Rotterdam scientists discovered that heterochromatin also acts as a protective layer during DNA replication prior to cell division. Specifically, heterochromatin is formed when replication grinds to a halt, such as when there are not enough building blocks to make new DNA strands, Taneja and her colleagues discovered. Scientists call this replication stress. ‘The tight heterochromatin packing acts as a protective layer that prevents DNA from being damaged during replication stress,’ Taneja explained. Once replication stress subsides and the DNA copying process can resume, the heterochromatin packing is removed.
This new function of heterochromatin is important. It is new fundamental knowledge about how the human body works, and could also potentially play a role in cancer treatments. In fact, Taneja and colleagues saw that cancer cells that have more heterochromatin are less sensitive to certain forms of chemotherapy.
‘Chemotherapy works by inhibiting DNA replication. That works poorly when the replicating DNA is protected by heterochromatin,’ Taneja explained. ‘Now that we know how heterochromatin is formed and broken down at replicating DNA under stress, we see opportunities to remove heterochromatin in cancer cells and thereby make them sensitive to chemotherapy again,’ Taneja said. Initial experiments indeed show that this is possible.
For herself and her international peers, the discovery of the new function of chromatin is an eye-opener, Taneja says. One of the figureheads in her field, Prof. Susan Gasser, even wrote an article about it in Nature Cell Biology. Taneja: ‘This is huge. I expect a greater understanding of heterochromatin to be revealed as a protective layer for DNA, in the coming years.’
To make chromatin visible, Taneja and her team used a technique they developed themselves and patented. It’s called ChromStretch and succeeds in making chromatin visible at the single molecular level.
This study was supported by the ERC and VIDI funds to Dr. Nitika Taneja.