Biography and research overview
Dr Peter Martin leads a highly collaborative research project, that explores the role of the multi-functional replication checkpoint protein topoisomerase beta binding protein 1 (TOPBP1) in mitosis. He undertook his PhD at the University of Salford after securing the Pathway to Excellence studentship, before joining the Genome Instability and Cancer Team. Dr Martin was awarded the BBSRC Discovery Fellowship to undertake a multidisciplinary research project within the Division of Cancer Biology.
Faithful and accurate division of the genome is vital to prevent damage during every cell cycle. However, cells often acquire DNA entanglements that are observed in mitosis as 'chromatin bridges', linking separating daughter cells, a sub-set of which are termed ultra-fine anaphase bridges (UFBs). If not resolved in a timely manner these bridges are a significant threat to the stability of the genome.
Previously, it was shown that TOPBP1 interacts with topoisomerase 2 alpha (TOP2A), the major human protein associated with the resolution of DNA entanglements in mitosis, and recruits TOP2A to UFBs. Inhibition of TOP2A with doxorubicin or etoposide have become established anti-cancer therapeutic strategies. However, resistance to TOP2A inhibitors as well as bone marrow and cardiac associated toxicity become a therapeutic problem. Dr Martin aims to determine the basis of the TOPBP1 and TOP2A interaction, paving the way towards development of novel anti-cancer therapeutic approaches that directly target mitosis with decreased off target toxicity and increased efficacy.
In collaboration with the Functional Proteomics team, Gene Function team and Division of Structural Biology, Dr Martin is systematically characterising the role of TOPBP1 and its mitotic proteome to provide novel insight into the molecular mechanism of UFB resolution and chromosomal disjunction. The Genome Instability and Cancer Team is the ideal environment for this project, with their extensive expertise in deciphering the molecular processes that underpin genome stability in cells.
Dr Martin aims to establish how healthy and dysfunctional cells facilitate faithful transmission of genetic information to daughter cells, which is necessary for the continuation of all multicellular life.