Naoko Shima, Ph.D.

Assistant Professor

Department of Genetics, Cell Biology & Development

Saitama University, Ph.D., 1996

Office phone: 612--626-7830
Lab phone: 612-626-7831

shima023@umn.edu

Research Interests:

Replication stress, chromosome instability, cancer

To discover new genes that affect chromosome stability and tumor susceptibility in mice, we have previously conducted a mouse mutagenesis screen. Using a highly sensitive flow cytometric assay that 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. Polq has two paralogs, Poln and Hel308. We are planning to investigate these paralogs’ functions in genome maintenance. Mcm4 is an essential gene that is required for eukaryotic DNA replication. Mice homozygous for a hypomorphic Mcm4 mutation are prone to spontaneous tumors. We are currently investigating the connection among replication stress, chromosome instability, and cancer using this novel mutant as a model.

Publications:

  • 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 T.R., Andrews C.A., Munroe R.J., Hartford S.A., Tye B.K., and Schimenti J.C. 2007. A viable allele of Mcm4 causes chromosome instability and mammary adenocarcinomas in mice. Nat. Genet. 39: 93-98.
  • Shima, N., Munroe, R.J. and Schimenti, J.C. 2004. The mouse genomic instability mutation chaos1 is an allele of Polq that exhibits genetic interaction with Atm. Mol. Cell. Biol. 23:10381-10389.
  • Shima, N., Hartford, S.A., Duffy, T., Wilson, L.A., Schimenti, K.J. and Schimenti, J.C. 2003. Phenotype-based identification of mouse chromosome instability mutants. Genetics 163:1031-1040.

Updated: June 9, 2008