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- Title
Two sequential cleavage reactions on cruciform DNA structures cause palindrome-mediated chromosomal translocations.
- Authors
Inagaki, Hidehito; Ohye, Tamae; Kogo, Hiroshi; Tsutsumi, Makiko; Kato, Takema; Tong, Maoqing; Emanuel, Beverly S.; Kurahashi, Hiroki
- Abstract
Gross chromosomal rearrangements (GCRs), such as translocations, deletions or inversions, are often generated by illegitimate repair between two DNA breakages at regions with nucleotide sequences that might potentially adopt a non-B DNA conformation. We previously established a plasmid-based model system that recapitulates palindrome-mediated recurrent chromosomal translocations in humans, and demonstrated that cruciform DNA conformation is required for the translocation-like rearrangements. Here we show that two sequential reactions that cleave the cruciform structures give rise to the translocation: GEN1-mediated resolution that cleaves diagonally at the four-way junction of the cruciform and Artemis-mediated opening of the subsequently formed hairpin ends. Indeed, translocation products in human sperm reveal the remnants of this two-step mechanism. These two intrinsic pathways that normally fulfil vital functions independently, Holliday-junction resolution in homologous recombination and coding joint formation in rearrangement of antigen-receptor genes, act upon the unusual DNA conformation in concert and lead to a subset of recurrent GCRs in humans.
- Publication
Nature Communications, 2013, Vol 4, Issue 3, p1592
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/ncomms2595