A paper in the December issue of Nature Chemical Biology reports a small molecule that suppresses the phenotype of a zebrafish mutation. Zebrafish are an increasingly popular model organism because they can be readily manipulated genetically and grow very quickly, allowing rapid in vivo analysis of mutation phenotypes.
Zebrafish have proven amenable to whole-organism chemical screening. Genes involved in the cell-cycle are very similar in zebrafish and humans, making zebrafish an easy system for studying genes affecting cell division, a process which is often compromised in cancer. Leonard Zon and colleagues have combined the power of genetics and chemical screening to identify a chemical suppressor of a specific cell-cycle mutation.
In a previous publication, the authors identified a zebrafish mutation called crash&burn (crb) that results in decreased expression of the key cell-cycle regulator cyclin B1 and causes mitotic arrest and genome instability. The team have now conducted a large-scale chemical screen and identified a compound, persynthamide, which suppresses the crb phenotype. The small molecule was shown to act by delaying progression through S phase of the cell cycle, the time when DNA is replicated before cell division. However, the precise molecular target of the small molecule remains to be identified.
In addition to providing a valuable new lead for a mitotic modulator, the use of zebrafish to identify a cell-cycle regulator raises the possibility of using transgenic zebrafish to screen directly for chemical suppressors of cancers that arise from cell-cycle defects.
Leonard I. Zon (HHMI and Harvard Medical School, Boston, MA, USA)
Abstract available online: Zon Paper.
(C) Nature Chemical Biology press release.
Message posted by: Trevor M. D'Souza