Formation of a G-quadruplex at the BCL2 major breakpoint region of the t(14;18) translocation in follicular lymphoma

Nambiar, Mridula ; Goldsmith, G. ; Moorthy, Balaji T. ; Lieber, Michael R. ; Joshi, Mamata V. ; Choudhary, Bibha ; Hosur, Ramakrishna V. ; Raghavan, Sathees C. (2011) Formation of a G-quadruplex at the BCL2 major breakpoint region of the t(14;18) translocation in follicular lymphoma Nucleic Acids Research, 39 (3). pp. 936-948. ISSN 0305-1048

Full text not available from this repository.

Official URL: http://nar.oxfordjournals.org/content/39/3/936.sho...

Related URL: http://dx.doi.org/10.1093/nar/gkq824

Abstract

The t(14;18) translocation in follicular lymphoma is one of the most common chromosomal translocations. Most breaks on chromosome 18 are located at the 3'-UTR of the BCL2 gene and are mainly clustered in the major breakpoint region (MBR). Recently, we found that the BCL2 MBR has a non-B DNA character in genomic DNA. Here, we show that single-stranded DNA modeled from the template strand of the BCL2 MBR, forms secondary structures that migrate faster on native PAGE in the presence of potassium, due to the formation of intramolecular G-quadruplexes. Circular dichroism shows evidence for a parallel orientation for G-quadruplex structures in the template strand of the BCL2 MBR. Mutagenesis and the DMS modification assay confirm the presence of three guanine tetrads in the structure. 1H nuclear magnetic resonance studies further confirm the formation of an intramolecular G-quadruplex and a representative model has been built based on all of the experimental evidence. We also provide data consistent with the possible formation of a G-quadruplex structure at the BCL2 MBR within mammalian cells. In summary, these important features could contribute to the single-stranded character at the BCL2 MBR, thereby contributing to chromosomal fragility.

Item Type:Article
Source:Copyright of this article belongs to Oxford University Press.
ID Code:80107
Deposited On:31 Jan 2012 04:22
Last Modified:31 Jan 2012 04:22

Repository Staff Only: item control page