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Cancer Genes and Genomics

Micronuclei Bearing Acentric Extrachromosomal Chromatin Are Transcriptionally Competent and May Perturb the Cancer Cell Phenotype

Graduate School of Biosphere Science, Hiroshima University, Higashi-hiroshima, Japan

^* To whom correspondence should be addressed. E-mail: shimizu{at}hiroshima-u.ac.jp.

	Abstract

Extrachromosomal double minutes (DM) bear amplified genes that contribute to the malignancy of human cancer cells. A novel intracellular behavior of DMs resulted in their selective entrapment within micronuclei; opening the vista, this could perturb the cancer cell phenotype if genes located on DMs were expressed in micronuclei. Here, using fluorescence in situ hybridization, we detected transcripts in DM-enriched micronuclei. Visualization of DMs and their transcripts in live cells showed that DMs are as actively transcribed in the micronuclei and nuclei. Moreover, pulse-incorporated bromouridine was detected in the micronuclei, and the transcripts eventually exited from the micronuclei, similar to the behavior of nuclear transcripts. This apparently normal pattern of gene expression in DM-enriched micronuclei was restricted to micronuclei associated with lamin B, and lamin B association was more frequent for micronuclei that incorporated DMs than for those that incorporated a chromosome arm. The frequency of lamin B-associated micronuclei increased after entry into S phase, and accordingly, there was a concomitant increase in transcription in micronuclei. Taken together, these results indicate that the expression of genes on DMs can be temporally altered by their incorporation into micronuclei. This may be relevant for a broad spectrum of other extrachromosomal elements. (Mol Cancer Res 2007;5(7):695-704)

Key Words: double minutes, micronucleus, transcription, lamin, extrachromosomal element