Gregory Ira, Ph.D.
Associate Professor, Department of Molecular & Human Genetics
Ph.D., Copernicus University
Postdoc, Brandeis University
DNA recombination is ubiquitous and essential for DNA-based life. Recombination repairs DNA gaps and breaks that occur during replication or are induced in meiosis. Mutation in human genes involved in homologous recombination results in genome instability and diseases including a large fraction of inherited breast and ovarian cancers, Nijmegen breakage syndrome, ataxia telangiectasia, Bloom syndrome, Fanconi Anemia, Rothmund-Thomson syndrome, and others. Eukaryotes show a very high degree of conservation of mechanisms and protein components of recombination. This offers a great potential for using model organisms to study DNA recombination processes. We use budding yeast, given the extensive genetic and molecular approaches available.
Our research goal is to understand the molecular mechanisms of homologous recombination and the role different proteins play during recombination. More specifically we are focusing on the function of DNA helicases and newly identified in genetic screen proteins in DNA repair. The main experimental model is recombination induced by a single double-strand-break. This assay allows us to follow the kinetics of all steps in recombination at the level of DNA strand exchange and protein-DNA interaction. The results from our projects will constitute the foundation for studying DNA recombination in human cells and will provide insight into molecular basis of genetic instability observed in cancer.
Malkova A, Ira G. (2013) Break-induced replication: functions and molecular mechanism.Curr Opin Genet Dev.2013 Jun;23(3):271-9.
- Wilson MA, Kwon Y, Xu Y, Chung WH, Chi P, Niu H, Mayle R, Chen X, Malkova A, Sung P, Ira G (2013). ¬Pif1 helicase and Polδ promote recombination-coupled DNA synthesis via bubble migration. Nature, Sep 27;489(7417):576-80
- Chen X, Cui D, Papusha A, Zhang X, Chu C-D, Tang J, Chen K, Pan X, Ira G (2012). The Fun30 nucleosome remodeler promotes resection of DNA double-strand break ends. Nature 489(7417): 576-80. PubMed PMID: 22960743
- Chen X, Niu H, Chung WH, Zhu Z, Papusha A, Shim EY, Lee SE, Sung P, Ira G (2011). Cell cycle regulation of DNA double-strand break end resection by Cdk1-dependent Dna2 phosphorylation. Nat. Struct. Mol. Biol. 18(9): 1015-9. PubMed PMID: 21841787
- Niu H, Chung WH, Zhu Z, Kwon Y, Zhao W, Chi P, Prakash R, Seong C, Liu D, Lu L, Ira G*, Sung P* (2010). Mechanism of the ATP-dependent DNA end-resection machinery from Saccharomyces cerevisiae. Nature 467(7311): 108-11. *corresponding authors. PubMed PMID: 20811460
- Prakash R, Satory D, Dray E, Papusha A, Scheller J, Kramer W, Krejci L, Klein H, Haber JE, Sung P, Ira G (2009). Yeast Mph1 helicase dissociates Rad51-made D-loops; implications for crossover control in mitotic recombination. Genes Dev. 23 (1): 67-79. PubMed PMID: 19136626
- Zhu Z, Chung WH, Shim EY, Lee SE, Ira G (2008). Sgs1 helicase and two nucleases Dna2 and Exo1 resect DNA double strand break ends. Cell 134(6): 981-94. PubMed PMID: 18805091
- Ira G, Pellicioli A, Balijja A, Wang X, Fiorani S, Carotenuto W, Liberi G, Bressan D, Wan L, Hollingsworth NM, Haber JE, Foiani M (2004). DNA end resection, homologous recombination and DNA damage checkpoint activation require CDK1. Nature 431(7011): 1011-7. PubMed PMID: 15496928
- Ira G, Malkova A, Liberi G, Foiani M, Haber JE (2003). Srs2 and Sgs1-Top3 suppress crossovers during double-strand break repair in yeast. Cell 115(4): 401-11. PubMed PMID: 14622595
For more publications, see listing on PubMed.
Gregory Ira, Ph.D.
Department of Molecular and Human Genetics
Baylor College of Medicine
One Baylor Plaza, MS BCM225
Houston, TX, 77030, U.S.A.