Researchers from David Horn's lab working with colleagues at the University of Sussex, have made a breakthrough in our understanding of how enzymes that make DNA, complete genome replication. Scientists studied a pair of primase polymerase-like (PPL) enzymes in the African trypanosome, a protozoan parasite that causes important diseases of humans and animals. These enzymes are also found in mammalian cells and many other eukaryotes.
Dr. Lucy Glover (joint first author on the report) and Prof. David Horn, both of whom moved to Dundee from the London School of Hygiene and Tropical Medicine (University of London) earlier this year, worked with Prof. Aidan Doherty and colleagues from the University of Sussex.
One PPL enzyme was found to be essential for parasite survival and the essential function was found to be in completing the replication of genomic DNA. In other work, this function was found to be shared with the human equivalent enzyme.
PPL2 can bypass DNA damage that accumulates during the bulk of DNA replication and we can now say that the previously known primase and polymerase enzymes fail to effectively fulfil this role without one of these PPL enzymes.
The findings have major implications for our understanding of DNA replication and repair, processes that are fundamental to life and commonly disrupted in diseases such as cancer.
Prof. David Horn said, "This is a great example of how work on trypanosomes can reveal potentially druggable parasite biology and, at the same time, yield important insight into conserved processes operating in human cells”.
The work was funded by grant support from the Wellcome Trust, the BBSRC and the MRC and is published in the journal Molecular Cell in November 2013.
PPL2 translesion polymerase is essential for the completion of chromosomal DNA replication in the African trypanosome (2013) Rudd, S., Glover, L., Jozwiakowski, S.K., Horn, D., & Doherty, A.J. Molecular Cell. 52: 554–565.