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

shima023@umn.edu
612-626-7830 — office
612-626-7831 — lab

Dr. Shima received her Ph.D. at Saitama University in Japan in 1996. She conducted postdoctoral fellowships at York University in Canada and The Jackson Laboratory 1997-2004, followed by a one-year position as a research associate at Cornell University. She joined the faculty in the Department of Genetics, Cell Biology & Development in 2005.

Research Interests

Dr. Shima's 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

Kawabata T, Yamaguchi S, Buske T, Luebben SW, Matise I, Wallace, M, Schimenti JC, Shima N.  A reduction of dormant origins reveals strain-specific replication dynamics in mice. Mamm Genome, 2011;22:506-517.

Kawabata T, Luebben SW, Yamaguchi S, Ilves I, Matise I, Buske T, Botchan MR, Shima N. Stalled fork rescue via dormant replication origins in unchallenged S phase promotes proper chromosome segregation and tumor suppression. Mol Cell 2011;41:543-553.

Steere, NH, Yamaguchi S, Andrews CA, Liachko I, Nakamura, T, Shima N. Functional screen of human MCM2-7 variant alleles for disease-causing potential, Mutat Res. 2009;666:74-78

Shima N, Buske TR, and Schimenti JC. Genetic screen for chromosome instability in mice: Mcm4 and breast cancer, Cell Cycle 2007;6:1135-114.

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.