Mitomycin C-induced pairing of heterochromatin reflects initiation of DNA repair and chromatid exchange formation.
- Resource Type
- Article
- Authors
- Abdel-Halim, H. I.; Natarajan, A. T.; Mullenders, L. H. F.; Boei, J. J. W. A.
- Source
- Journal of Cell Science. 4/15/2005, Vol. 118 Issue 8, p1757-1767. 11p.
- Subject
- *DNA repair
*MITOMYCIN C
*HETEROCHROMATIN
*SISTER chromatid exchange
*CHROMOSOME replication
*GENETIC recombination
*DNA
*GENETICS
- Language
- ISSN
- 0021-9533
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. [ABSTRACT FROM AUTHOR]