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First published online 29 March 2005
doi: 10.1242/jcs.02306

Journal of Cell Science 118, 1757-1767 (2005)
Published by The Company of Biologists 2005
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Research Article

Mitomycin C-induced pairing of heterochromatin reflects initiation of DNA repair and chromatid exchange formation

H. I. Abdel-Halim1,2, A. T. Natarajan1, L. H. F. Mullenders1,* and J. J. W. A. Boei1

1 Department of Toxicogenetics, Leiden University Medical Center, PO Box 9503, 2300 RA Leiden, The Netherlands
2 Department of Zoology, Faculty of Sciences, Suez Canal University, Ismailia, Egypt

* Author for correspondence (e-mail: l.mullenders{at}lumc.nl)

Accepted 3 February 2005

Chromatid interchanges induced by the DNA cross-linking agent mitomycin C (MMC) are over-represented in human chromosomes containing large heterochromatic regions. We found that nearly all exchange breakpoints of chromosome 9 are located within the paracentromeric heterochromatin and over 70% of exchanges involving chromosome 9 are between its homologues. We provide evidence that the required pairing of chromosome 9 heterochromatic regions occurs in G0/G1 and S-phase cells as a result of an active cellular process initiated upon MMC treatment. By contrast, no pairing was observed for a euchromatic paracentromeric region of the equal-sized chromosome 8. The MMC-induced pairing of chromosome 9 heterochromatin is observed in a subset of cells; its percentage closely mimics the frequency of homologous interchanges found at metaphase. Moreover, the absence of pairing in cells derived from XPF patients correlates with an altered spectrum of MMC-induced exchanges. Together, the data suggest that the heterochromatin-specific pairing following MMC treatment reflects the initiation of DNA cross-link repair and the formation of exchanges.

Key words: Chromosome pairing, Chromosome positioning, Cross-link repair, Heterochromatin, MMC, XPF


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