{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T15:03:57Z","timestamp":1758121437950},"reference-count":49,"publisher":"The Company of Biologists","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2005,4,15]]},"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.1242\/jcs.02306","type":"journal-article","created":{"date-parts":[[2005,3,30]],"date-time":"2005-03-30T01:23:58Z","timestamp":1112145838000},"page":"1757-1767","source":"Crossref","is-referenced-by-count":10,"title":["Mitomycin C-induced pairing of heterochromatin reflects initiation of DNA repair and chromatid exchange formation"],"prefix":"10.1242","volume":"118","author":[{"given":"H. I.","family":"Abdel-Halim","sequence":"first","affiliation":[{"name":"Department of Toxicogenetics, Leiden University Medical Center, PO Box 9503, 2300 RA Leiden, The Netherlands"},{"name":"Department of Zoology, Faculty of Sciences, Suez Canal University, Ismailia, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. T.","family":"Natarajan","sequence":"additional","affiliation":[{"name":"Department of Toxicogenetics, Leiden University Medical Center, PO Box 9503, 2300 RA Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L. H. F.","family":"Mullenders","sequence":"additional","affiliation":[{"name":"Department of Toxicogenetics, Leiden University Medical Center, PO Box 9503, 2300 RA Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. J. W. A.","family":"Boei","sequence":"additional","affiliation":[{"name":"Department of Toxicogenetics, Leiden University Medical Center, PO Box 9503, 2300 RA Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","reference":[{"key":"2021042519161136600_REF1","doi-asserted-by":"crossref","unstructured":"Abdel-Halim, H. I., Imam, S. A., Badr, F. M., Natarajan, A. T.,\n          Mullenders, L. H. F. and Boei, J. J. W. A. (2004). Ionizing radiation induced instant pairing of heterochromatin of homologous chromosomes in human cells. Cytogenet. Genome Res.104, 193-199.","DOI":"10.1159\/000077488"},{"key":"2021042519161136600_REF2","doi-asserted-by":"crossref","unstructured":"Adair, G. M., Rolig, R. L., Moore-Faver, D., Zabelshanksy, M., Wilson, J.\n          H. and Nairn, R. S. (2000). Role of ERCC1 in removal of long non-homologous tails during targeted homologous recombination. EMBO J.19, 5552-5561.","DOI":"10.1093\/emboj\/19.20.5552"},{"key":"2021042519161136600_REF3","doi-asserted-by":"crossref","unstructured":"Arnoldus, E. P., Peters, A. C. B., Bots, G. T. A. M., Raap, A. K. and van der Ploeg, M. (1989). Somatic pairing of chromosome 1 centromeres in interphase nuclei of human cerebellum. Hum. Genet.83, 231-234.","DOI":"10.1007\/BF00285162"},{"key":"2021042519161136600_REF4","doi-asserted-by":"crossref","unstructured":"Boei, J. J. W. A., Vermeulen, S. and Natarajan, A. T. (1996). Detection of chromosomal aberrations by fluorescence in situ hybridization in the first three postirradiation divisions of human lymphocytes. Mutat. Res.349, 127-135.","DOI":"10.1016\/0027-5107(95)00171-9"},{"key":"2021042519161136600_REF5","doi-asserted-by":"crossref","unstructured":"Borowy-Borowski, H., Lipman, R. and Tomasz, M. (1990). Recognition between mitomycin C and specific DNA sequences for cross-link formation. Biochem.29, 2999-3006.","DOI":"10.1021\/bi00464a016"},{"key":"2021042519161136600_REF6","doi-asserted-by":"crossref","unstructured":"Brogger, A. and Johansen, J. (1972). A model for the production of chromosome damage by mitomycin C. Chromosoma (Berl.).38, 95-104.","DOI":"10.1007\/BF00319957"},{"key":"2021042519161136600_REF7","doi-asserted-by":"crossref","unstructured":"Carr, A., Schmidt, H., Kirchhoff, S., Muriel, W., Sheldrick, K.,\n          Griffiths, D., Basmacioglu, C., Subramani, S., Clegg, M. and Nasim, A. (1994). The rad16 gene of Schizosaccharomyces pombe: a homolog of the RAD1 gene of Saccharomyces cerevisiae. Mol. Cell. Biol.14, 2029-2040.","DOI":"10.1128\/MCB.14.3.2029"},{"key":"2021042519161136600_REF8","doi-asserted-by":"crossref","unstructured":"Chipchase, M. D. and Melton, D. W. (\n          2002). The formation of UV-induced chromosome aberrations involves ERCC1 and XPF but not other nucleotide excision repair genes. DNA Repair1, 335-340.","DOI":"10.1016\/S1568-7864(02)00010-1"},{"key":"2021042519161136600_REF9","doi-asserted-by":"crossref","unstructured":"Darroudi, F., Fomina, J., Meijers, M. and Natarajan, A. T. (1998). Kinetics of the formation of chromosome aberrations in X-irradiated human lymphocytes, using PCC and FISH. Mutat. Res.404, 55-65.","DOI":"10.1016\/S0027-5107(98)00095-5"},{"key":"2021042519161136600_REF10","doi-asserted-by":"crossref","unstructured":"De Silva, I. U., McHugh, P. J., Clingen, P. H. and Hartley, J. A. (2000). Defining the roles of nucleotide excision repair and recombination in the repair of DNA interstrand cross-links in mammalian cells. Mol. Cell. Biol.20, 7980-7990.","DOI":"10.1128\/MCB.20.21.7980-7990.2000"},{"key":"2021042519161136600_REF11","doi-asserted-by":"crossref","unstructured":"De Silva, I. U., McHugh, P. J., Clingen, P. H. and Hartley, J. A. (2002). Defects in interstrand cross-link uncoupling do not account for the extreme sensitivity of ERCC1 and XPF cells to cisplatin. Nucleic Acids Res.30, 3848-3856.","DOI":"10.1093\/nar\/gkf479"},{"key":"2021042519161136600_REF12","unstructured":"Dorr, R., Browen, G. T. and Alberts, D. S. (1985). Interaction of mitomycin C with mammalian DNA detected by alkaline elution. Cancer Res.45, 3510-3516."},{"key":"2021042519161136600_REF13","doi-asserted-by":"crossref","unstructured":"Dronkert, M. L. G. and Kanaar, R. (2001). Repair of DNA interstrand cross-links. Mutat. Res.486, 217-247.","DOI":"10.1016\/S0921-8777(01)00092-1"},{"key":"2021042519161136600_REF14","doi-asserted-by":"crossref","unstructured":"Fung, J. C., Marshall, W. F., Dernburg, A., Agard, D. A. and Sedat, J. W. (1998). Homologous chromosome pairing in Drosophila melanogaster proceeds through multiple independent initiations. J. Cell Biol.141, 5-20.","DOI":"10.1083\/jcb.141.1.5"},{"key":"2021042519161136600_REF15","doi-asserted-by":"crossref","unstructured":"Gosden, J. R., Mitchell, A. R., Buckland, R. A., Clayton, R. P. and Evans,\n          H. J. (1975). The location of four human satellite DNAs on human chromosomes. Exp. Cell Res.92, 148-158.","DOI":"10.1016\/0014-4827(75)90648-5"},{"key":"2021042519161136600_REF16","unstructured":"Haaf, T., Steinlein, K. and Schmid, M. (1986). Preferential somatic pairing between homologous heterochromatic regions of human chromosomes. Am. J. Hum. Genet.38, 319-329."},{"key":"2021042519161136600_REF17","doi-asserted-by":"crossref","unstructured":"Henikoff, S. (1997). Nuclear organization and gene expression: homologous pairing and long-range interactions. Curr. Opin. Cell Biol.9, 388-395.","DOI":"10.1016\/S0955-0674(97)80012-9"},{"key":"2021042519161136600_REF18","doi-asserted-by":"crossref","unstructured":"Hoogstraten, D., Nigg, A. L., Heath, H., Mullenders, L. H. F., van Driel,\n          R., Hoeijmakers, J. H. J., Vermeulen, W. and Houtsmuller, A. B. (2002). Rapid switching of TFIIH between RNA polymerase I and II transcription and DNA repair in vivo. Mole. Cell10, 1163-1174.","DOI":"10.1016\/S1097-2765(02)00709-8"},{"key":"2021042519161136600_REF19","doi-asserted-by":"crossref","unstructured":"Iyer, V. N. and Szybalski, W. (1963). A molecular mechanism of mitomycin action: linking of complimentary strands. Proc. Natl. Acad. Sci. USA50, 355-362.","DOI":"10.1073\/pnas.50.2.355"},{"key":"2021042519161136600_REF20","doi-asserted-by":"crossref","unstructured":"Johnson, W. S., He, Q.-Y. and Tomasz, M. (1995). Selective recognition of the m5CpG dinucleotide sequence in DNA by mitomycin C for alkylation and cross-linking. Bioorg. Med. Chem.3, 851-860.","DOI":"10.1016\/0968-0896(95)00067-Q"},{"key":"2021042519161136600_REF21","doi-asserted-by":"crossref","unstructured":"Jolly, C., Konencny, L., Grady, D. L., Kutskova, Y. A., Cotto, J. J.,\n          Morimoto, R. I. and Vourc'h, C. (2002). In vivo binding of active heat shock transcription factor 1 to human chromosome 9 heterochromatin during stress. J. Cell Biol.156, 775-781.","DOI":"10.1083\/jcb.200109018"},{"key":"2021042519161136600_REF22","doi-asserted-by":"crossref","unstructured":"Joseph, J. L., Brasch, J. M. and Smyth, D. R. (1982a). Patterns of exchange induced by mitomycin C in C-bands of human chromosomes. I. Relationship to C-band size in chromosomes 1, 9, and 16. Hum. Genet.62, 342-345.","DOI":"10.1007\/BF00304552"},{"key":"2021042519161136600_REF23","doi-asserted-by":"crossref","unstructured":"Joseph, J. L., Brasch, J. M. and Smyth, D. R. (1982b). Patterns of exchange induced by mitomycin C in C-bands of human chromosomes. II. High frequency of Y-Y exchange in XYY cells. Hum. Genet.62, 346-348.","DOI":"10.1007\/BF00304553"},{"key":"2021042519161136600_REF24","doi-asserted-by":"crossref","unstructured":"Keyes, S. R., Loomis, R., Digiovanna, M. P., Pritsos, C. A., Rockwell, S. and Sartorelli, A. C. (1991). Cytotoxicity and DNA cross-links produced by mitomycin analogs in aerobic and hypoxic EMT6 cells. Cancer Commun.3, 351-356.","DOI":"10.3727\/095535491820873812"},{"key":"2021042519161136600_REF25","doi-asserted-by":"crossref","unstructured":"Koch, C. and Stra\u0308tling, W. H. (2004). DNA binding of methyl-CpG-binding protein MeCP2 in human MCF7 cells. Biochemistry43, 5011-5021.","DOI":"10.1021\/bi0359271"},{"key":"2021042519161136600_REF26","doi-asserted-by":"crossref","unstructured":"LaSalle, J. M. and Lalande, M. (1996). Homologous association of oppositely imprinted chromosomal domains. Science272, 725-728.","DOI":"10.1126\/science.272.5262.725"},{"key":"2021042519161136600_REF27","doi-asserted-by":"crossref","unstructured":"Lewis, J. P., Tanke, H. J., Raap, A. K., Beverstock, G. C. and Kluin-Nelemans, H. C. (1993). Somatic pairing of centromeres and short arms of chromosome 15 in the hematopoietic and lymphoid system. Hum. Genet.92, 577-582.","DOI":"10.1007\/BF00420942"},{"key":"2021042519161136600_REF28","doi-asserted-by":"crossref","unstructured":"Li, V.-S., Reed, M., Zheng, Y., Kohn, H. and Tang, M.-S. (2000). C5 cytosine methylation at CpG sites enhances sequence selectivity of mitomycin C-DNA bonding. Biochemistry39, 2612-2618.","DOI":"10.1021\/bi991307h"},{"key":"2021042519161136600_REF29","doi-asserted-by":"crossref","unstructured":"Li, V.-S., Tang, M.-S. and Kohn, H. (2001). The effect of C(5) cytosine methylation at CpG sequences on mitomycin-DNA bonding profiles. Bioorg. Med. Chem.9, 863-873.","DOI":"10.1016\/S0968-0896(00)00301-1"},{"key":"2021042519161136600_REF30","doi-asserted-by":"crossref","unstructured":"Loidl, J. (1990). The initiation of meiotic chromosome pairing: the cytological view. Genome33, 759-778.","DOI":"10.1139\/g90-115"},{"key":"2021042519161136600_REF31","doi-asserted-by":"crossref","unstructured":"Marshall, W. F., Straight, A., Marko, J. F., Swedlow, J., Dernburg, A.,\n          Belmont, A., Murray, A. W., Agard, D. A. and Sedat, J. W. (1997). Interphase chromosomes undergo constrained diffusional motion in living cells. Curr. Biol.7, 930-939.","DOI":"10.1016\/S0960-9822(06)00412-X"},{"key":"2021042519161136600_REF32","doi-asserted-by":"crossref","unstructured":"Melton, D. W., Ketchen, A.-M., Nunez, F., Bonatti-Abbondandolo, S.,\n          Abbondandolo, A., Squires, S. and Johnson, R. T. (1998). Cells from ERCC1-deficient mice show increased genome instability and a reduced frequency of S-phase-dependent illegitimate chromosome exchange but a normal frequency of homologous recombination. J. Cell Sci.111, 395-404.","DOI":"10.1242\/jcs.111.3.395"},{"key":"2021042519161136600_REF33","doi-asserted-by":"crossref","unstructured":"Meneveri, R., Agresti, A., Marozzi, A., Saccone, S., Rocchi, M.,\n          Archidiacono, N., Corneo, G., Valle, G. D. and Ginelli, E. (1993). Molecular organization and chromosomal location of human GC-rich heterochromatic blocks. Gene123, 227-234.","DOI":"10.1016\/0378-1119(93)90128-P"},{"key":"2021042519161136600_REF34","doi-asserted-by":"crossref","unstructured":"Miller, O. J., Schnedl, W., Allen, J. and Erlanger, B. F. (1974). 5-methylcytosine localised in mammalian constitutive heterochromatin. Nature251, 636-637.","DOI":"10.1038\/251636a0"},{"key":"2021042519161136600_REF35","doi-asserted-by":"crossref","unstructured":"Morad, M., Jonasson, J. and Lindsten, J. (1973). Distribution of mitomycin C induced breaks on human chromosomes. Hereditas74, 273-282.","DOI":"10.1111\/j.1601-5223.1973.tb01128.x"},{"key":"2021042519161136600_REF36","doi-asserted-by":"crossref","unstructured":"Morton, N. E. (1991). Parameters of the human genome. Proc. Natl. Acad. Sci. USA88, 7474-7476.","DOI":"10.1073\/pnas.88.17.7474"},{"key":"2021042519161136600_REF37","doi-asserted-by":"crossref","unstructured":"Mu, D., Bessho, T., Nechev, L. V., Chen, D. J., Harris, T. M., Hearst, J. E. and Sancar, A. (2000). DNA interstrand cross-links induce futile repair synthesis in mammalian cell extracts. Mol. Cell. Biol.20, 2446-2454.","DOI":"10.1128\/MCB.20.7.2446-2454.2000"},{"key":"2021042519161136600_","doi-asserted-by":"crossref","unstructured":"Niedenhofer, L. J., Essers, J., Weeda, G., Beverloo, B., de Wit, J.,\n          Muijtjens, M., Odijk, H., Hoeijmakers, J. H. and Kanaar, R. (2001). The structure-specific endonuclease Ercc1-Xpf is required for targeted gene replacement in embryonic stem cells. EMBO J.20, 6540-6549.","DOI":"10.1093\/emboj\/20.22.6540"},{"key":"2021042519161136600_REF39","doi-asserted-by":"crossref","unstructured":"Rothfuss, A. and Grompe, M. (2004). Repair kinetics of genomic interstrand DNA cross-links: Evidence for DNA double-strand break-dependent activation of the Fanconi Anemia\/BRCA pathway. Mol. Cell. Biol.24, 123-134.","DOI":"10.1128\/MCB.24.1.123-134.2004"},{"key":"2021042519161136600_REF40","doi-asserted-by":"crossref","unstructured":"Sargent, R. G., Meservy, J. L., Perkins, B. D., Kilburn, A. E., Intody, Z.,\n          Adair, G. M., Nairn, R. S. and Wilson, J. H. (2000). Role of the nucleotide excision repair gene ERCC1 in formation of recombination-dependent rearrangements in mammalian cells. Nucleic Acids Res.28, 3771-3778.","DOI":"10.1093\/nar\/28.19.3771"},{"key":"2021042519161136600_REF41","doi-asserted-by":"crossref","unstructured":"Schmid, M., Poppen, A., Schmid, W. and Engel, W. (1981). Somatic pairings of the Y heterochromatin in human XYY and Xyqi cells. Cytogenet. Cell Genet.29, 203-214.","DOI":"10.1159\/000131571"},{"key":"2021042519161136600_REF42","doi-asserted-by":"crossref","unstructured":"Sekelsky, J. J., McKim, K. S., Chin, G. M. and Hawley, R. S. (1995). The Drosophila meiotic recombination gene mei-9 encodes a homologue of the yeast excision repair protein Rad1. Genetics141, 619-627.","DOI":"10.1093\/genetics\/141.2.619"},{"key":"2021042519161136600_REF43","doi-asserted-by":"crossref","unstructured":"Shaw, M. W. and Cohen, M. M. (1965). Chromosome exchanges in human leukocytes induced by mitomycin C. Genetics51, 181-190.","DOI":"10.1093\/genetics\/51.2.181"},{"key":"2021042519161136600_REF44","unstructured":"Stout, K., van der Maarel, S., Frants, R. R., Padberg, G. W., Roperts, H.\n          H. and Haaf, T. (1999). Somatic pairing between sub-telomeric chromosome regions: implications for human genetic disease? Chrom. Res.7, 323-329."},{"key":"2021042519161136600_REF45","doi-asserted-by":"crossref","unstructured":"Sun, H. B. and Yokota, H. (1999). Correlated positioning of homologous chromosomes in daughter fibroblast cells. Chromosome Res.7, 603-610.","DOI":"10.1023\/A:1009279918034"},{"key":"2021042519161136600_REF46","doi-asserted-by":"crossref","unstructured":"Sun, H. B., Shen, J. and Yokota, H. (2000). Size-dependent positioning of human chromosomes in interphase nuclei. Biophys. J.79, 184-190.","DOI":"10.1016\/S0006-3495(00)76282-5"},{"key":"2021042519161136600_REF47","doi-asserted-by":"crossref","unstructured":"Teng, S. P., Woodson, S. A. and Crothers, D. M. (1989). DNA sequence specificity of mitomycin cross-linking. Biochemistry28, 3901-3907.","DOI":"10.1021\/bi00435a041"},{"key":"2021042519161136600_REF48","doi-asserted-by":"crossref","unstructured":"Verweij, J. and Pinedo, H. M. (1990). Mitomycin C: mechanism of action, usefullness and limitation. Anti-Cancer Drugs1, 5-13.","DOI":"10.1097\/00001813-199010000-00002"},{"key":"2021042519161136600_REF49","doi-asserted-by":"crossref","unstructured":"Williams, B. J., Jones, E. and Brothman, R. (1995). Homologous centromere association of chromosomes 9 and 17 in prostate cancer. Cancer Genet. Cytogenet.58, 143-152.","DOI":"10.1016\/0165-4608(95)00150-6"}],"container-title":["Journal of Cell Science"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/journals.biologists.com\/jcs\/article-pdf\/118\/8\/1757\/1520722\/1757.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/journals.biologists.com\/jcs\/article-pdf\/118\/8\/1757\/1520722\/1757.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,4,25]],"date-time":"2021-04-25T20:01:37Z","timestamp":1619380897000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/jcs\/article\/118\/8\/1757\/28749\/Mitomycin-C-induced-pairing-of-heterochromatin"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,4,15]]},"references-count":49,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2005,4,15]]}},"URL":"https:\/\/doi.org\/10.1242\/jcs.02306","relation":{},"ISSN":["1477-9137","0021-9533"],"issn-type":[{"value":"1477-9137","type":"electronic"},{"value":"0021-9533","type":"print"}],"subject":[],"published":{"date-parts":[[2005,4,15]]}}}