DNA structural basis for fragility at peak III of BCL2 major breakpoint region associated with t(14;18) translocation

Javadekar, Saniya M and Yadav, Rakhee and Raghavan, Sathees C (2018) DNA structural basis for fragility at peak III of BCL2 major breakpoint region associated with t(14;18) translocation. In: BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS, 1862 (3). pp. 649-659.

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Abstract

Maintaining genome integrity is crucial for normal cellular functions. DNA double-strand breaks (DSBs), when unrepaired, can potentiate chromosomal translocations. t(14;18) translocation involving BCL2 gene on chromosome 18 and IgH loci at chromosome 14, could lead to follicular lymphoma. Molecular basis for fragility of translocation breakpoint regions is an active area of investigation. Previously, formation of non-B DNA structures like G-quadruplex, triplex, B/A transition were investigated at peak I of BCL2 major breakpoint region (MBR); however, it is less understood at peak III. In vitro gel shift assays show faster mobility for MBR peak III sequences, unlike controls. CD studies of peak III sequences reveal a spectral pattern different from B-DNA. Although complementary C-rich stretches exhibit single-strandedness, corresponding guanine-rich sequences do not show DMS protection, ruling out G-quadruplex and triplex DNA. Extrachromosomal assay indicates that peak III halts transcription, unlike its mutated version. Taken together, multiple lines of evidence suggest formation of potential cruciform DNA structure at MBR peak III, which was also supported by in silico studies. Thus, our study reveals formation of non-B DNA structure which could be a basis for fragility at BCL2 breakpoint regions, eventually leading to chromosomal translocations.

Item Type:	Journal Article
Publication:	BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
Publisher:	ELSEVIER SCIENCE BV, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
Additional Information:	Copy right for the article belong to ELSEVIER SCIENCE BV, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
Department/Centre:	Division of Biological Sciences > Biochemistry
Date Deposited:	08 Mar 2018 19:09
Last Modified:	08 Mar 2018 19:09
URI:	http://eprints.iisc.ac.in/id/eprint/59107

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