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Molecular and Cellular Biology, December 2004, p. 10448-10455, Vol. 24, No. 23
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.23.10448-10455.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Deficiency in SNM1 Abolishes an Early Mitotic Checkpoint Induced by Spindle Stress{dagger}

Shamima Akhter,1 Christopher T. Richie,1,{ddagger} Jian Min Deng,1 Eric Brey,2 Xiaoshan Zhang,1 Charles Patrick Jr.,2 Richard R. Behringer,1 and Randy J. Legerski1*

Department of Molecular Genetics,1 Department of Plastic Surgery, The University of Texas M. D. Anderson Cancer Center, Houston, Texas2

Received 28 June 2004/ Returned for modification 20 July 2004/ Accepted 6 September 2004

Spindle poisons represent an important class of anticancer drugs that act by interfering with microtubule polymerization and dynamics and thereby induce mitotic checkpoints and apoptosis. Here we show that mammalian SNM1 functions in an early mitotic stress checkpoint that is distinct from the well-characterized spindle checkpoint that regulates the metaphase-to-anaphase transition. Specifically, we found that compared to wild-type cells, Snm1-deficient mouse embryonic fibroblasts exposed to spindle poisons exhibited elevated levels of micronucleus formation, decreased mitotic delay, a failure to arrest in mitosis prior to chromosome condensation, supernumerary centrosomes, and decreased viability. In addition, we show that both Snm1 and 53BP1, previously shown to interact, coimmunoprecipitate with components of the anaphase-promoting complex (APC)/cyclosome. These findings suggest that Snm1 is a component of a mitotic stress checkpoint that negatively targets the APC prior to chromosome condensation.

* Corresponding author. Mailing address: University of Texas M. D. Anderson Cancer Center, Department of Molecular Genetics, 1515 Holcombe Blvd., Houston, TX 77030. Phone: (713) 792-8941. Fax: (713) 794-4295. E-mail: rlegersk{at}mdanderson.org.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

{ddagger} Present address: National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 20892.

Molecular and Cellular Biology, December 2004, p. 10448-10455, Vol. 24, No. 23
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.23.10448-10455.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Hejna, J., Philip, S., Ott, J., Faulkner, C., Moses, R. (2007). The hSNM1 protein is a DNA 5'-exonuclease. Nucleic Acids Res 35: 6115-6123 [Abstract] [Full Text]  
  • Freibaum, B. D., Counter, C. M. (2006). hSnm1B Is a Novel Telomere-associated Protein. J. Biol. Chem. 281: 15033-15036 [Abstract] [Full Text]  
  • Ahkter, S., Richie, C. T., Zhang, N., Behringer, R. R., Zhu, C., Legerski, R. J. (2005). Snm1-Deficient Mice Exhibit Accelerated Tumorigenesis and Susceptibility to Infection. Mol. Cell. Biol. 25: 10071-10078 [Abstract] [Full Text]  
  • Ward, I. M., Difilippantonio, S., Minn, K., Mueller, M. D., Molina, J. R., Yu, X., Frisk, C. S., Ried, T., Nussenzweig, A., Chen, J. (2005). 53BP1 Cooperates with p53 and Functions as a Haploinsufficient Tumor Suppressor in Mice. Mol. Cell. Biol. 25: 10079-10086 [Abstract] [Full Text]  


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