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Genetic analysis of Homologous recombination in the Archaea - New insights into DNA Double-Strand Break Repair by Rad50/Mre11

Reference	BB/C501641/1
Principal Investigator / Supervisor	Professor Thorsten Allers
Co-Investigators / Co-Supervisors
Institution	University of Nottingham
Department	Sch of Biology
Funding type	Research
Value (£)	229,997
Status	Completed
Type	Research Grant
Start date	10/01/2005
End date	09/01/2008
Duration	36 months

Abstract

Homologous recombination is a fundamental process that rearranges genes, repairs damaged DNA and underpins replication. Our understanding of recombination stems from studies of Escherichia coli and Saccharomyces cerevisiae, which have served well as models of bacterial and eukaryotic systems, respectively. We have developed Haloferax volcanii as a model organism for archaeal genetics, to study DNA double-strand break repair in this poorly-characterised domain of life. A central role in DNA double-strand break repair is played by the Mre11-Rad50 protein complex. In eukaryotes, mutations in mre11 or rad50 result in DNA damage sensitivity. Homologues of Mre11 and Rad50 are present in all domains of life, with similar biochemical properties. However, fundamental questions remain about the function of Mre11 ¿Rad50 in vivo. The role of Mre11 ¿Rad50 in archaea will be investigated using genetic tools such as heteroallele recombination and plasmid end-joining assays. Since archaeal DNA processing resembles the more complex systems found in eukaryotes, Haloferax volcanii may provide a simple test bed to explore problems that remain intractable in higher organisms. Mismatched bases formed during recombination are corrected by the same machinery that repairs errors made during DNA replication. Mismatch repair proteins also serve to impose a barrier to interspecies recombination. Haloferax volcanii mutL and mutS mutants will be tested for their effect on both DNA mismatch repair and recombination between divergent sequences. This is expected to reveal how archaea maintain genetic fidelity in the harsh environments they occupy, and to throw light on the role of lateral gene transfer in archaeal evolution.

Summary

unavailable

Committee	Closed Committee - Genes & Developmental Biology (GDB)
Research Topics	X – not assigned to a current Research Topic
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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