Nucleic Acids Research Advance Access originally published online on January 30, 2007
Nucleic Acids Research 2007 35(4):1198-1208; doi:10.1093/nar/gkm036
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Nucleic Acids Research, 2007, Vol. 35, No. 4 1198-1208
© 2007 The Author(s).
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Molecular Biology |
Cruciform extrusion propensity of human translocation-mediating palindromic AT-rich repeats
1Division of Molecular Genetics, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Aichi 470-1192, Japan, 221st Century COE Program, Development Center for Targeted and Minimally Invasive Diagnosis and Treatment, Fujita Health University, Toyoake, Aichi 470-1192, Japan, 3Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA and 4Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
*To whom correspondence should be addressed. Tel: +81 562 939391; Fax: +81 562 938831; Email: kura{at}fujita-hu.ac.jp
Received August 27, 2006. Revised November 28, 2006. Accepted January 8, 2007.
There is an emerging consensus that secondary structures of DNA have the potential for genomic instability. Palindromic AT-rich repeats (PATRRs) are a characteristic sequence identified at each breakpoint of the recurrent constitutional t(11;22) and t(17;22) translocations in humans, named PATRR22 (
600 bp), PATRR11 (450 bp) and PATRR17 (190 bp). The secondary structure-forming propensity in vitro and the instability in vivo have been experimentally evaluated for various PATRRs that differ regarding their size and symmetry. At physiological ionic strength, a cruciform structure is most frequently observed for the symmetric PATRR22, less often for the symmetric PATRR11, but not for the other PATRRs. In wild-type E. coli, only these two PATRRs undergo extensive instability, consistent with the relatively high incidence of the t(11;22) in humans. The resultant deletions are putatively mediated by central cleavage by the structure-specific endonuclease SbcCD, indicating the possibility of a cruciform conformation in vivo. Insertion of a short spacer at the centre of the PATRR22 greatly reduces both its cruciform extrusion in vitro and instability in vivo. Taken together, cruciform extrusion propensity depends on the length and central symmetry of the PATRR, and is likely to determine the instability that leads to recurrent translocations in humans.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  A. M. Casper, P. W. Greenwell, W. Tang, and T. D. Petes Chromosome Aberrations Resulting From Double-Strand DNA Breaks at a Naturally Occurring Yeast Fragile Site Composed of Inverted Ty Elements Are Independent of Mre11p and Sae2p Genetics, October 1, 2009; 183(2): 423 - 439. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Kurahashi, H. Inagaki, T. Kato, E. Hosoba, H. Kogo, T. Ohye, M. Tsutsumi, H. Bolor, M. Tong, and B. S. Emanuel Impaired DNA replication prompts deletions within palindromic sequences, but does not induce translocations in human cells Hum. Mol. Genet., September 15, 2009; 18(18): 3397 - 3406. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Inagaki, T. Ohye, H. Kogo, T. Kato, H. Bolor, M. Taniguchi, T. H. Shaikh, B. S. Emanuel, and H. Kurahashi Chromosomal instability mediated by non-B DNA: Cruciform conformation and not DNA sequence is responsible for recurrent translocation in humans Genome Res., February 1, 2009; 19(2): 191 - 198. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Kato, H. Inagaki, H. Kogo, T. Ohye, K. Yamada, B. S. Emanuel, and H. Kurahashi Two different forms of palindrome resolution in the human genome: deletion or translocation Hum. Mol. Genet., April 15, 2008; 17(8): 1184 - 1191. [Abstract] [Full Text] [PDF]
|
|