Imperial College London

DrMarcoDi Antonio

Faculty of Natural SciencesDepartment of Chemistry

BBSRC Fellow
 
 
 
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Contact

 

+44 (0)20 7594 5866m.di-antonio

 
 
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Location

 

207LMolecular Sciences Research HubWhite City Campus

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Summary

 

Publications

Citation

BibTex format

@article{Sengar:2019:nar/gky1179,
author = {Sengar, A and Vandana, JJ and Chambers, VS and Di, Antonio M and Winnerdy, FR and Balasubramanian, S and Phan, AT},
doi = {nar/gky1179},
journal = {Nucleic Acids Res},
pages = {1564--1572},
title = {Structure of a (3+1) hybrid G-quadruplex in the PARP1 promoter.},
url = {http://dx.doi.org/10.1093/nar/gky1179},
volume = {47},
year = {2019}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - Poly (ADP-ribose) polymerase 1 (PARP1) has emerged as an attractive target for cancer therapy due to its key role in DNA repair processes. Inhibition of PARP1 in BRCA-mutated cancers has been observed to be clinically beneficial. Recent genome-mapping experiments have identified a non-canonical G-quadruplex-forming sequence containing bulges within the PARP1 promoter. Structural features, like bulges, provide opportunities for selective chemical targeting of the non-canonical G-quadruplex structure within the PARP1 promoter, which could serve as an alternative therapeutic approach for the regulation of PARP1 expression. Here we report the G-quadruplex structure formed by a 23-nucleotide G-rich sequence in the PARP1 promoter. Our study revealed a three-layered intramolecular (3+1) hybrid G-quadruplex scaffold, in which three strands are oriented in one direction and the fourth in the opposite direction. This structure exhibits unique structural features such as an adenine bulge and a G·G·T base triple capping structure formed between the central edgewise loop, propeller loop and 5' flanking terminal. Given the highly important role of PARP1 in DNA repair and cancer intervention, this structure presents an attractive opportunity to explore the therapeutic potential of PARP1 inhibition via G-quadruplex DNA targeting.
AU - Sengar,A
AU - Vandana,JJ
AU - Chambers,VS
AU - Di,Antonio M
AU - Winnerdy,FR
AU - Balasubramanian,S
AU - Phan,AT
DO - nar/gky1179
EP - 1572
PY - 2019///
SP - 1564
TI - Structure of a (3+1) hybrid G-quadruplex in the PARP1 promoter.
T2 - Nucleic Acids Res
UR - http://dx.doi.org/10.1093/nar/gky1179
UR - https://www.ncbi.nlm.nih.gov/pubmed/30551210
VL - 47
ER -