University of Minnesota
University of Minnesota
College of Biological Sciences
http://www.cbs.umn.edu/

Naoko Shima, PhD

Asssociate Professor
612-626-7830
PhD: Saitama University, Japan, 1996

Research Techniques:

Mouse embryonic stem culture; Gene Knockout/Knockin; Cytogenetics; Cell cycle; Flow cytometric analysis of chromosome breaks

 


Research Interests:

Dr. Shima's laboratory uses the Laboratory Mouse as a model system 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, they 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, they 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. The Lab is planning to investigate these paralogs’ function in genome maintenance.

Mcm4 is an essential gene that is required for DNA replication. Dr. Shima's lab has recovered a hypomorphic allele of Mcm4, which could cause replication defect or stress.  These mutant mice are highly prone to mammary tumors. They 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.  Mammalian Genome, in press.

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

Steere, NH, Yamaguchi S, Andrews CA, Liachko I, Nakamura, T, Shima N (2009) Functional screen of human MCM2-7 variant alleles for disease-causing potential, Mutat Res, 666(1-2) 74-78

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

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

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

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

Reinholdt R, Ashley T, Schimenti J, Shima N (2003) Forward genetic screens for meiotic and mitotic recombination-defective mutants, In Genetic Recombination, Reviews and Protocols edited by Waldman AS, Methods in Molecular Biology, Humana Press, Totowa, NJ

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

Office:
6-136 MCB

Lab:
6-156 MCB
P: 612-626-7831