Bell, NAW;
Haynes, PJ;
Brunner, K;
de Oliveira, TM;
Flocco, MM;
Hoogenboom, BW;
Molloy, JE;
(2021)
Single-molecule measurements reveal that PARP1 condenses DNA by loop stabilization.
Science Advances
, 7
(33)
, Article eabf3641. 10.1126/sciadv.abf3641.
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Abstract
Poly(ADP-ribose) polymerase 1 (PARP1) is an abundant nuclear enzyme that plays important roles in DNA repair, chromatin organization and transcription regulation. Although binding and activation of PARP1 by DNA damage sites has been extensively studied, little is known about how PARP1 binds to long stretches of undamaged DNA and how it could shape chromatin architecture. Here, using single-molecule techniques, we show that PARP1 binds and condenses undamaged, kilobase-length DNA subject to sub-piconewton mechanical forces. Stepwise decondensation at high force and DNA braiding experiments show that the condensation activity is due to the stabilization of DNA loops by PARP1. PARP inhibitors do not affect the level of condensation of undamaged DNA but act to block condensation reversal for damaged DNA in the presence of NAD+. Our findings suggest a mechanism for PARP1 in the organization of chromatin structure.
| Type: | Article |
|---|---|
| Title: | Single-molecule measurements reveal that PARP1 condenses DNA by loop stabilization |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1126/sciadv.abf3641 |
| Publisher version: | https://doi.org/10.1126/sciadv.abf3641 |
| Language: | English |
| Additional information: | Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY). |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Physics and Astronomy |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10132993 |
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