Congratulations are due to Marija Maric, who has just been awarded the Pontecorvo Prize for 2014, for her discovery that the end of chromosome replication is regulated by ubiquitylation and the p97 ATPase. Marija completed her PhD studies last year in Karim Labib's group, and was funded by Cancer Research UK (CRUK).
The Pontecorvo Prize is a prestigious national award for the best PhD thesis supported by CRUK each year. The panel were particularly impressed by Marija's paper in the journal Science last year, (Maric et al, 2014, Cdc48 and a ubiquitin ligase drive disassembly of the CMG helicase at the end of DNA replication - click here to read), which opens up a whole new area of research into how the final stages of chromosome replication are controlled by ubiquitylation.
Chromosome replication is regulated in an exquisite fashion, in order to ensure that it only occurs once per cell cycle, thus allowing the stable inheritance of the genome from one generation to another. At the heart of this regulation is the DNA helicase that unwinds the parental DNA duplex. The helicase can only be assembled on its DNA substrate once per cell cycle, as cells enter S-phase, and the helicase then remains stably associated with DNA replication forks until the replication process has been completed. Marija found that the helicase is then ubiquitylated on just one of its 11 subunits, leading to a disassembly reaction that requires the Cdc48/p97 segregase. This work raises many important questions for future studies of the mechanism and regulation of chromosome replication in eukaryotic cells. It will be interesting to identify the ubiquitin ligase that controls the DNA helicase in human cells, with the ultimate aim of testing whether inhibition of this ligase might selectively kill cancer cells.
The Pontecorvo prize is associated with an honorarium and a free place at the next conference of the National Cancer Research Institute. Marija will also be expected to give a talk about her work at the next national CRUK student meeting. The funding for the prize was provided by Professor Peter Goodfellow FRS, and the award is named after the geneticist Professor Guido Pontecorvo, who worked at the Lincoln's Inn Field laboratories of CRUK's London Research Institute from 1968-1975. Marija will remain with Karim's group at the MRC-PPU until later this year, before starting a postdoc in Simon Boulton's lab at the Francis Crick Institute.
The Pontecorvo Prize is a prestigious national award for the best PhD thesis supported by CRUK each year. The panel were particularly impressed by Marija's paper in the journal Science last year, (Maric et al, 2014, Cdc48 and a ubiquitin ligase drive disassembly of the CMG helicase at the end of DNA replication - click here to read), which opens up a whole new area of research into how the final stages of chromosome replication are controlled by ubiquitylation.
Chromosome replication is regulated in an exquisite fashion, in order to ensure that it only occurs once per cell cycle, thus allowing the stable inheritance of the genome from one generation to another. At the heart of this regulation is the DNA helicase that unwinds the parental DNA duplex. The helicase can only be assembled on its DNA substrate once per cell cycle, as cells enter S-phase, and the helicase then remains stably associated with DNA replication forks until the replication process has been completed. Marija found that the helicase is then ubiquitylated on just one of its 11 subunits, leading to a disassembly reaction that requires the Cdc48/p97 segregase. This work raises many important questions for future studies of the mechanism and regulation of chromosome replication in eukaryotic cells. It will be interesting to identify the ubiquitin ligase that controls the DNA helicase in human cells, with the ultimate aim of testing whether inhibition of this ligase might selectively kill cancer cells.
The Pontecorvo prize is associated with an honorarium and a free place at the next conference of the National Cancer Research Institute. Marija will also be expected to give a talk about her work at the next national CRUK student meeting. The funding for the prize was provided by Professor Peter Goodfellow FRS, and the award is named after the geneticist Professor Guido Pontecorvo, who worked at the Lincoln's Inn Field laboratories of CRUK's London Research Institute from 1968-1975. Marija will remain with Karim's group at the MRC-PPU until later this year, before starting a postdoc in Simon Boulton's lab at the Francis Crick Institute.