Two sequential cleavage reactions on cruciform DNA structures cause palindrome-mediated chromosomal translocations

Hidehito Inagaki, Tamae Ohye, Hiroshi Kogo, Makiko Tsutsumi, Takema Kato, Maoqing Tong, Beverly S. Emanuel and Hiroki Kurahashi ()
Additional contact information
Hidehito Inagaki: Institute for Comprehensive Medical Science, Fujita Health University
Tamae Ohye: Institute for Comprehensive Medical Science, Fujita Health University
Hiroshi Kogo: Institute for Comprehensive Medical Science, Fujita Health University
Makiko Tsutsumi: Institute for Comprehensive Medical Science, Fujita Health University
Takema Kato: Institute for Comprehensive Medical Science, Fujita Health University
Maoqing Tong: Institute for Comprehensive Medical Science, Fujita Health University
Beverly S. Emanuel: The Children’s Hospital of Philadelphia
Hiroki Kurahashi: Institute for Comprehensive Medical Science, Fujita Health University

Nature Communications, 2013, vol. 4, issue 1, 1-10

Abstract: 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.

Date: 2013
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms2595 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms2595

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms2595

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().