The fruitfly Drosophila melanogaster is one of the best genetic model organisms for a large number of research areas in modern biology. However , one of the most useful genetic tools has been prominently missing for Drosophila, that is the ability to target specific genes for mutation by homologous recombination. Gene targeting has, for over twenty years, allowed yeast and mouse researchers to introduce specific mutations to essentially any gene. Such a tool is especially important for gene function studies in organisms with a completely sequenced genome. Dr. Rong was the main driving force for the recent development of a gene targeting method in Drosophila. Such method has allowed Drosophila researchers worldwide to successfully mutate many different loci that were not previously identified in traditional mutant screens. As a demonstration of the general applicability of the method, Dr. Rong knocked out the Drosophila homolog of the tumor suppressor p53 in collaboration with Dr. Gerald Rubin's group. Characterization of the mutant phenotype of the Drosophila mutant is in progress. The main research interest of Dr. Rong's group is to study the mechanisms for DNA double strand break repair in Drosophila. To facilitate such a study, Dr. Rong has introduced a site-specific double strand break system into Drosophila in which one can control the position of the break, the number of breaks, the timing of breakage, and the genomic environment surrounding the break. Using this system, Dr. Rong was able to provide evidence suggesting that genomic structure around the DNA break dictates the choice of not only the repair mechanism but also the template for repair. A goal of the lab is to combine the power of the site-specific breakage system and the gene targeting method to elucidate the function of gene products involved in the repair of these DNA lesions. The work of Dr. Rong's group would contribute to a better understanding of how eukaryotic organisms maintain the physical integrity of their genomes.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC010446-09
Application #
8175320
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
9
Fiscal Year
2010
Total Cost
$1,010,685
Indirect Cost
Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code
Yamanaka, Soichiro; Mehta, Sameet; Reyes-Turcu, Francisca E et al. (2013) RNAi triggered by specialized machinery silences developmental genes and retrotransposons. Nature 493:557-60
Wesolowska, Natalia; Amariei, Flavia L; Rong, Yikang S (2013) Clustering and Protein Dynamics of Drosophila melanogaster Telomeres. Genetics 195:381-91
Yu, Zhongsheng; Ren, Mengda; Wang, Zhanxiang et al. (2013) Highly efficient genome modifications mediated by CRISPR/Cas9 in Drosophila. Genetics 195:289-91
Morciano, Patrizia; Zhang, Yi; Cenci, Giovanni et al. (2013) A hypomorphic mutation reveals a stringent requirement for the ATM checkpoint protein in telomere protection during early cell division in Drosophila. G3 (Bethesda) 3:1043-8
Wesolowska, Natalia; Rong, Yikang S (2013) Long-range targeted manipulation of the Drosophila genome by site-specific integration and recombinational resolution. Genetics 193:411-9
Zhang, Liang; Rong, Yikang S (2012) Retrotransposons at Drosophila telomeres: host domestication of a selfish element for the maintenance of genome integrity. Biochim Biophys Acta 1819:771-5
Kane, Daniel P; Shusterman, Michael; Rong, Yikang et al. (2012) Competition between replicative and translesion polymerases during homologous recombination repair in Drosophila. PLoS Genet 8:e1002659
Beaucher, Michelle; Zheng, Xiao-Feng; Amariei, Flavia et al. (2012) Multiple pathways suppress telomere addition to DNA breaks in the Drosophila germline. Genetics 191:407-17
Gao, Guanjun; Cheng, Yan; Wesolowska, Natalia et al. (2011) Paternal imprint essential for the inheritance of telomere identity in Drosophila. Proc Natl Acad Sci U S A 108:4932-7
Gao, Guanjun; Bi, Xiaolin; Chen, Jie et al. (2009) Mre11-Rad50-Nbs complex is required to cap telomeres during Drosophila embryogenesis. Proc Natl Acad Sci U S A 106:10728-33

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