Centromere mitotic recombination in mammalian cells.
Centromeres are special structures of eukaryotic chromosomes that hold sister chromatid together and ensure proper chromosome segregation during cell division. Centromeres consist of repeated sequences, which have hindered the study of centromere mitotic recombination and its consequences for centromeric function. We use a chromosome orientation fluorescence in situ hybridization technique to visualize and quantify recombination events at mouse centromeres. We show that centromere mitotic recombination occurs in normal cells to a higher frequency than telomere recombination and to a much higher frequency than chromosome-arm recombination. Furthermore, we show that centromere mitotic recombination is increased in cells lacking the Dnmt3a and Dnmt3b DNA methyltransferases, suggesting that the epigenetic state of centromeric heterochromatin controls recombination events at these regions. Increased centromere recombination in Dnmt3a,3b-deficient cells is accompanied by changes in the length of centromere repeats, suggesting that prevention of illicit centromere recombination is important to maintain centromere integrity in the mouse.
Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre, 28029 Madrid, Spain.
Isabel
I
Jaco
Andrés
A
Canela
Elsa
E
Vera
Maria A
MA
Blasco
D000818:Animals; D002503:Centromere / Q000235:genetics*; D033481:Chromosomes, Mammalian / Q000378:metabolism; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000172:deficiency; D019175:DNA Methylation; D004276:DNA, Satellite / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology / Q000201:enzymology; D005838:Genotype; D017404:In Situ Hybridization, Fluorescence; D051379:Mice; D008810:Mice, Inbred C57BL; D018598:Minisatellite Repeats; D008938:Mitosis / Q000235:genetics*; D011995:Recombination, Genetic / Q000235:genetics*; D012854:Sister Chromatid Exchange; D016615:Telomere / Q000378:metabolism
D004276:DNA, Satellite; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases