DNA Recombination Laboratory

Hideo Tsubouchi PhD - Group Leader

Sarah Farmer, PhD
Wing-Kit Leung, MSc

We have moved!

With immediate effect the DNA Recombination Laboratory has moved to the University of Sussex

Our new contact details are as follows:

Hideo Tsubouchi
Genome Damage and Stability Centre
Science Park Road
University of Sussex
Falmer, Brighton
East Sussex BN1 9RQ

Tel: +44(0)1273-678-123
Fax: +44(0)1273-678-121
Email: h.tsubouchi@sussex.ac.uk

Homologous recombination plays important roles in both somatic and the germ line cells.  The major role of homologous recombination in somatic cells is to repair breaks in DNA duplexes (DNA double-strand breaks, or DSBs).  This type of DNA damage is caused either internally, such as errors accompanying DNA replication, or externally by DNA damaging factors, such as cosmic rays. Among multiple pathways to repair DSBs, homologous recombination is the only way to repair them accurately. If homologous recombination becomes defective, cells can no longer maintain the integrity of their genetic material and become highly susceptible to cancer. Furthermore, in germ line cells where the number of chromosomes is halved to produce haploid gametes, homologous recombination is used to link and orient two homologous chromosomes.  Such recombination events are essential for the creation of reproductive cells that contain the appropriate number of chromosomes.  A defect in homologous recombination can result in gametes with an abnormal number of chromosomes, causing spontaneous abortion and birth defects such as Down's syndrome. Such chromosome missegregation is closely associated with some types of cancer.

Using yeast genetics as a powerful tool, I plan to focus my future research in the following three aspects of homologous recombination.

1.  The mechanism that directs DSBs to be repaired through homologous recombination.

2.  The mechanism responsible for the recognition of homology between DNA molecules, using the meiotic recombination machinery as a model.

3.  The mechanism to regulate the partner choice in homologous recombination.  Homologous recombination occurs predominantly between sister-chromatids in vegetative cells whereas interaction between homologs is promoted during meiosis.  What is the underlying mechanism?

Selected References

Busygina, V., Sehorn, M.G., Shi, I.Y., *Tsubouchi, H., Roeder, G.S. and *Sung, P. (2008)
Hed1 regulates Rad51-mediated recombination via a novel mechanism.
Genes Dev., 22: 786-795. online http://www.genesdev.org/cgi/doi/10.1101/gad.1638708

Tsubouchi, H. and G.S. Roeder (2006)
Budding yeast Hed1 down-regulates the mitotic recombination machinery when meiotic recombination is impaired.
Genes Dev., 20: 1766-1775.

Tsubouchi, H. and G.S. Roeder  (2004)
The budding yeast Mei5 and Sae3 proteins act in the Dmc1-dependent meiotic recombination pathway.
Genetics, 168: 1219-1230.

Tsubouchi, H. and G.S. Roeder  (2003)
The importance of genetic recombination for fidelity of chromosome pairing in meiosis.
Dev. Cell, 5: 915-925.

Tsubouchi, H. and G.S. Roeder  (2002)
The Mnd1 protein forms a complex with Hop2 to promote homologous chromosome pairing and meiotic double-strand break repair.
Mol. Cell. Biol., 22: 3078-3088.

*Corresponding authors