Double-strand break repair by interchromosomal recombination: suppression of chromosomal translocations.
To directly determine whether recombinational repair of double-strand breaks (DSBs) can occur between heterologous chromosomes and lead to chromosomal rearrangements in mammalian cells, we employed an ES cell system to analyze recombination between repeats on heterologous chromosomes. We found that recombination is induced at least 1000-fold following the introduction of a DSB in one repeat. Most (98%) recombinants repaired the DSB by gene conversion in which a small amount of sequence information was transferred from the unbroken chromosome onto the broken chromosome. The remaining recombinants transferred a larger amount of information, but still no chromosomal aberrations were apparent. Thus, mammalian cells are capable of searching genome-wide for sequences that are suitable for DSB repair. The lack of crossover events that would have led to translocations supports a model in which recombination is coupled to replication.
Richardson
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Cell Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center and Cornell University Graduate School of Medical Sciences, New York, New York 10021 USA.
Moynahan
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Jasin
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D000483:Alleles; D000818:Animals; D015139:Blotting, Southern; D002460:Cell Line; D002875:Chromosomes / Q000235:genetics; D003434:Crossing Over, Genetic; D004249:DNA Damage / Q000502:physiology*; D004260:DNA Repair / Q000235:genetics*; D004261:DNA Replication; D015252:Deoxyribonucleases, Type II Site-Specific / Q000378:metabolism; D005785:Gene Conversion / Q000235:genetics*; D020440:Gene Duplication; D017930:Genes, Reporter; D017404:In Situ Hybridization, Fluorescence; D051379:Mice; D008957:Models, Genetic; D009154:Mutation; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051573:Proto-Oncogene Proteins c-pim-1; D012689:Sequence Homology, Nucleic Acid; D014162:Transfection; D014178:Translocation, Genetic
D011518:Proto-Oncogene Proteins; C496636:Pim1 protein, mouse; D017346:Protein Serine-Threonine Kinases; D051573:Proto-Oncogene Proteins c-pim-1; D015252:Deoxyribonucleases, Type II Site-Specific