This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Shima, N. Articles by Schimenti, J. C. Search for Related Content PubMed PubMed Citation Articles by Shima, N. Articles by Schimenti, J. C.

The Mouse Genomic Instability Mutation chaos1 Is an Allele of Polq That Exhibits Genetic Interaction with Atm

Naoko Shima, Robert J. Munroe, and John C. Schimenti^*

The Jackson Laboratory, Bar Harbor, Maine

Received 21 July 2004/ Returned for modification 10 August 2004/ Accepted 19 August 2004

chaos1 (for chromosome aberrations occurring spontaneously 1) is a recessive mutation that was originally identified in a phenotype-based screen for chromosome instability mutants in mice. Mutant animals exhibit significantly higher frequencies of spontaneous and radiation- or mitomycin C-induced micronucleated erythrocytes, indicating a potential defect in homologous recombination or interstrand cross-link repair. The chaos1 allele was genetically associated with a missense mutation in Polq, which encodes DNA polymerase . We demonstrate here that chaos1 is a mutant allele of Polq by using two genetic approaches: chaos1 mutant phenotype correction by a bacterial artificial chromosome carrying wild-type Polq and a failed complementation test between chaos1 and a Polq-disrupted allele generated by gene targeting. To investigate the potential involvement of Polq in DNA double-strand break repair, we introduced chaos1 into an Atm (for ataxia telangiectasia mutated)-deficient background. The majority (90%) of double-homozygous mice died during the neonatal period. Surviving double mutants exhibited synergistic phenotypes such as severe growth retardation and enhanced chromosome instability. However, remarkably, double mutants had delayed onset of thymic lymphoma, significantly increasing life span. These data suggest a unique role of Polq in maintaining genomic integrity, which is probably distinctive from the major homologous recombination pathway regulated by ATM.

Present address: Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853.

This article has been cited by other articles:

• Arana, M. E., Seki, M., Wood, R. D., Rogozin, I. B., Kunkel, T. A. (2008). Low-fidelity DNA synthesis by human DNA polymerase theta. Nucleic Acids Res 36: 3847-3856 [Abstract] [Full Text]  
• Levitt, P. S., Zhu, M., Cassano, A., Yazinski, S. A., Liu, H., Darfler, J., Peters, R. M., Weiss, R. S. (2007). Genome Maintenance Defects in Cultured Cells and Mice following Partial Inactivation of the Essential Cell Cycle Checkpoint Gene Hus1. Mol. Cell. Biol. 27: 2189-2201 [Abstract] [Full Text]  
• Ukai, A., Maruyama, T., Mochizuki, S., Ouchida, R., Masuda, K., Kawamura, K., Tagawa, M., Kinoshita, K., Sakamoto, A., Tokuhisa, T., O-Wang, J. (2006). Role of DNA polymerase {theta} in tolerance of endogenous and exogenous DNA damage in mouse B cells. GENES CELLS 11: 111-121 [Abstract] [Full Text]  
• Masuda, K., Ouchida, R., Takeuchi, A., Saito, T., Koseki, H., Kawamura, K., Tagawa, M., Tokuhisa, T., Azuma, T., O-Wang, J. (2005). DNA polymerase {theta} contributes to the generation of C/G mutations during somatic hypermutation of Ig genes. Proc. Natl. Acad. Sci. USA 102: 13986-13991 [Abstract] [Full Text]  
• Cordes, S. P. (2005). N-Ethyl-N-Nitrosourea Mutagenesis: Boarding the Mouse Mutant Express. Microbiol. Mol. Biol. Rev. 69: 426-439 [Abstract] [Full Text]  
• Guy, C. P., Bolt, E. L. (2005). Archaeal Hel308 helicase targets replication forks in vivo and in vitro and unwinds lagging strands. Nucleic Acids Res 33: 3678-3690 [Abstract] [Full Text]  
• XU, Z., FULOP, Z., ZHONG, Y., EVINGER, A. J. III, ZAN, H., CASALI, P. (2005). DNA Lesions and Repair in Immunoglobulin Class Switch Recombination and Somatic Hypermutation. Ann. N. Y. Acad. Sci. 1050: 146-162 [Abstract] [Full Text]