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

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

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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:	Journal Article
Publication:	Nucleic Acids Research
Publisher:	Oxford University Press
Additional Information:	Copyright of this article belongs to Oxford University Press.
Department/Centre:	Division of Biological Sciences > Biochemistry
Date Deposited:	18 Mar 2011 10:37
Last Modified:	18 Mar 2011 10:37
URI:	http://eprints.iisc.ac.in/id/eprint/35990

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