Dr. Shima's research focuses on the 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 translation activity plays a crucial role in immunoglobulin gene somatic hypermutation, which underlies the generation of high-affinity antibodies. Polq has two paralogs Poln and Helq. 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 spontaneous tumors. They are currently investigating the connection among replication stress, chromosome instability, and cancer using this novel mutant as a model.
Selected Publications (Pubmed Search)
Luebben, S.W., Kawabata, T., Johnson, C.S., O'Sullivan, M.G., and Shima, N. (2014) A concomitant loss of dormant origins and FANCC exacerbates genome instability by impairing DNA replication fork progression, Nucleic Acids Res, 42:5605-5615
Luo, Y., Hartford, S.A., Zenga, R., Southarda, T.L., Shima, N., and Schimenti, J.C. (2014) Hypersensitivity of primordial germ cells to compromised replication-associated DNA repair involves ATM-p53-p21 signaling, PLOS Genetics, e1004471.
Luebben S.W., Kawabata T., Akre M.K., Lee W.L., Johnson C.S., O'Sullivan M.G., and Shima N. (2013) Helq acts in parallel to Fancc to suppress replication-associated genome instability. Nucleic Acids Res, 41:10283-10297
Kawabata T, Yamaguchi S, Buske T, Luebben SW, Matise I, Wallace, M, Schimenti JC, Shima N (2011). A reduction of dormant origins reveals strain-specific replication dynamics in mice. Mamm Genome 22: 506-517.
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.
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