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Molecular and Cellular Biology, December 2002, p. 8635-8647, Vol. 22, No. 24
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.24.8635-8647.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

hSnm1 Colocalizes and Physically Associates with 53BP1 before and after DNA Damage

Christopher T. Richie,1 Carolyn Peterson,1 Tao Lu,2 Walter N. Hittelman,2 Phillip B. Carpenter,3 and Randy J. Legerski1*

Department of Molecular Genetics,1 Department of Experimental Therapeutics, M. D. Anderson Cancer Center,2 Department of Biochemistry and Molecular Biology, University of Texas Health Sciences Center, Houston, Texas 770303

Received 21 March 2002/ Returned for modification 7 May 2002/ Accepted 19 September 2002

snm1 mutants of Saccharomyces cerevisiae have been shown to be specifically sensitive to DNA interstrand crosslinking agents but not sensitive to monofunctional alkylating agents, UV, or ionizing radiation. Five homologs of SNM1 have been identified in the mammalian genome and are termed SNM1, SNM1B, Artemis, ELAC2, and CPSF73. To explore the functional role of human Snm1 in response to DNA damage, we characterized the cellular distribution and dynamics of human Snm1 before and after exposure to DNA-damaging agents. Human Snm1 was found to localize to the cell nucleus in three distinct patterns. A particular cell showed diffuse nuclear staining, multiple nuclear foci, or one or two larger bodies confined to the nucleus. Upon exposure to ionizing radiation or an interstrand crosslinking agent, the number of cells exhibiting Snm1 bodies was reduced, while the population of cells with foci increased dramatically. Indirect immunofluorescence studies also indicated that the human Snm1 protein colocalized with 53BP1 before and after exposure to ionizing radiation, and a physical interaction was confirmed by coimmunoprecipitation assays. Furthermore, human Snm1 foci formed after ionizing radiation were largely coincident with foci formed by human Mre11 and to a lesser extent with those formed by BRCA1, but not with those formed by human Rad51. Finally, we mapped a region of human Snm1 of approximately 220 amino acids that was sufficient for focus formation when attached to a nuclear localization signal. Our results indicate a novel function for human Snm1 in the cellular response to double-strand breaks formed by ionizing radiation.

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

Molecular and Cellular Biology, December 2002, p. 8635-8647, Vol. 22, No. 24
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.24.8635-8647.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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