Research Program: Genetic Mechanisms of Cancer
Assistant Professor, Department of Genetics, Cell Biology and Development

shima023@tc.umn.edu
612-626-7830 — office
612-626-7831 — lab
Preferred method of contact: e-mail

Dr. Shima received her Ph.D. from Saitama University, Japan in 1996. She conducted her postdoctoral work first at York University in Canada (1997-2000) and then at the Jackson Laboratory/Cornell University (2000-2005). She joined the Department of Genetics, Cell Biology and Development at the University of Minnesota as an assistant professor in 2005.

Research Interests

My laboratory uses the laboratory mouse as a model organism to investigate the connection between chromosome instability and cancer. To discover new genes or novel alleles that potentially affect chromosome stability and tumor susceptibility in mice, we have previously conducted a whole-animal mutagenesis screen. Using a highly sensitive flow cytometric assay that efficiently detects chromosome breaks in blood cells, several mutations were recovered. By positional cloning and subsequent genetic experiments, we have identified mutations in two genes, Polq and Mcm4.

Polq encodes DNA polymerase theta, a polymerase unique in that it also possesses a helicase domain in a single polypeptide. POLQ is an error-prone polymerase that can efficiently bypass an abasic site. This translesion activity plays a crucial role in immunoglobulin gene somatic hypermutation, which underlies the generation of high-affinity antibodies. Polq has two paralogs. We are planning to investigate these paralogs' function in genome maintenance.

Mcm4 is an essential gene that is required for DNA replication. We have recovered a hypomorphic allele of Mcm4, which could cause replication defect or stress. These mutant mice are highly prone to mammary tumors. We are currently investigating the connection among replication stress, chromosome instability, and cancer using this novel mutant as a model.

Selected Publications

Shima N, Buske TR, and Schimenti JC. Genetic screen for chromosome instability in mice: Mcm4 and breast cancer. Cell Cycle 2007;6:1135-4110.

Shima N, Alcaraz A, Liachko I, Buske TR, Anderws CA, Munroe RJ, Hartford SA, Tye BK, Schimenti JC. A viable allele of Mcm4 causes chromosome instability and mammary adenocarcinomas in mice. Nat Genet. 2007;39: 93-98.

Zan H, Shima N, Xu Z, Al-Qahtani A, Evinger III AJ, Zhong Y, Schimenti JC, Casali P. The translesion DNA polymerase theta plays a dominant role in immunoglobulin gene somatic hypermutation, EMBO J. 2005;24: 3757-3769.

Shima N, Munroe RJ, Schimenti JC. The mouse genomic instability mutation chaos1 is an allele of Polq that exhibits genetic interaction with Atm, Mol Cell Biol. 2004;23:10381-10389.

Shima N, Hartford SA, Duffy T, Wilson LA, Schimenti KJ, Schimenti JC. Phenotype-based identification of mouse chromosome instability mutants, Genetics 2003;163:1031-1040.