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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
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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 |