Human RECQ1 promotes restart of replication forks reversed by DNA topoisomerase I inhibition

Topoisomerase I (TOP1) inhibitors are an important class of anticancer drugs. The cytotoxicity of TOP1 inhibitors can be modulated by replication fork reversal, in a process that requires PARP activity. Whether regressed forks can efficiently restart and the factors required to restart fork progress...

Full description

Bibliographic Details
Main Authors:	Berti, Matteo, Chaudhuri, Arnab Ray, Thangavel, Saravanabhavan, Gomathinayagam, Shivasankari, Kenig, Sasa, Vujanovic, Marko, Odreman, Federico, Glatter, Timo, Graziano, Simona, Mendoza-Maldonado, Ramiro, Marino, Francesca, Lucic, Bojana, Biasin, Valentina, Gstaiger, Matthias, Aebersold, Ruedi, Sidorova, Julia M., Monnat, Raymond J., Lopes, Massimo, Vindigni, Alessandro
Format:	Online
Language:	English
Published:	2013
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3897332/

id	pubmed-3897332
recordtype	oai_dc
spelling	pubmed-38973322014-01-21 Human RECQ1 promotes restart of replication forks reversed by DNA topoisomerase I inhibition Berti, Matteo Chaudhuri, Arnab Ray Thangavel, Saravanabhavan Gomathinayagam, Shivasankari Kenig, Sasa Vujanovic, Marko Odreman, Federico Glatter, Timo Graziano, Simona Mendoza-Maldonado, Ramiro Marino, Francesca Lucic, Bojana Biasin, Valentina Gstaiger, Matthias Aebersold, Ruedi Sidorova, Julia M. Monnat, Raymond J. Lopes, Massimo Vindigni, Alessandro Article Topoisomerase I (TOP1) inhibitors are an important class of anticancer drugs. The cytotoxicity of TOP1 inhibitors can be modulated by replication fork reversal, in a process that requires PARP activity. Whether regressed forks can efficiently restart and the factors required to restart fork progression after fork reversal are still unknown. Here we combined biochemical and electron microscopy approaches with single-molecule DNA fiber analysis, to identify a key role for human RECQ1 helicase in replication fork restart after TOP1 inhibition, not shared by other human RecQ proteins. We show that the poly(ADPribosyl)ation activity of PARP1 stabilizes forks in their regressed state by limiting their restart by RECQ1. These studies provide new mechanistic insights into the roles of RECQ1 and PARP in DNA replication and offer molecular perspectives to potentiate chemotherapeutic regimens based on TOP1 inhibition. 2013-02-10 2013-03 /pmc/articles/PMC3897332/ /pubmed/23396353 http://dx.doi.org/10.1038/nsmb.2501 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Berti, Matteo Chaudhuri, Arnab Ray Thangavel, Saravanabhavan Gomathinayagam, Shivasankari Kenig, Sasa Vujanovic, Marko Odreman, Federico Glatter, Timo Graziano, Simona Mendoza-Maldonado, Ramiro Marino, Francesca Lucic, Bojana Biasin, Valentina Gstaiger, Matthias Aebersold, Ruedi Sidorova, Julia M. Monnat, Raymond J. Lopes, Massimo Vindigni, Alessandro
spellingShingle	Berti, Matteo Chaudhuri, Arnab Ray Thangavel, Saravanabhavan Gomathinayagam, Shivasankari Kenig, Sasa Vujanovic, Marko Odreman, Federico Glatter, Timo Graziano, Simona Mendoza-Maldonado, Ramiro Marino, Francesca Lucic, Bojana Biasin, Valentina Gstaiger, Matthias Aebersold, Ruedi Sidorova, Julia M. Monnat, Raymond J. Lopes, Massimo Vindigni, Alessandro Human RECQ1 promotes restart of replication forks reversed by DNA topoisomerase I inhibition
author_facet	Berti, Matteo Chaudhuri, Arnab Ray Thangavel, Saravanabhavan Gomathinayagam, Shivasankari Kenig, Sasa Vujanovic, Marko Odreman, Federico Glatter, Timo Graziano, Simona Mendoza-Maldonado, Ramiro Marino, Francesca Lucic, Bojana Biasin, Valentina Gstaiger, Matthias Aebersold, Ruedi Sidorova, Julia M. Monnat, Raymond J. Lopes, Massimo Vindigni, Alessandro
author_sort	Berti, Matteo
title	Human RECQ1 promotes restart of replication forks reversed by DNA topoisomerase I inhibition
title_short	Human RECQ1 promotes restart of replication forks reversed by DNA topoisomerase I inhibition
title_full	Human RECQ1 promotes restart of replication forks reversed by DNA topoisomerase I inhibition
title_fullStr	Human RECQ1 promotes restart of replication forks reversed by DNA topoisomerase I inhibition
title_full_unstemmed	Human RECQ1 promotes restart of replication forks reversed by DNA topoisomerase I inhibition
title_sort	human recq1 promotes restart of replication forks reversed by dna topoisomerase i inhibition
description	Topoisomerase I (TOP1) inhibitors are an important class of anticancer drugs. The cytotoxicity of TOP1 inhibitors can be modulated by replication fork reversal, in a process that requires PARP activity. Whether regressed forks can efficiently restart and the factors required to restart fork progression after fork reversal are still unknown. Here we combined biochemical and electron microscopy approaches with single-molecule DNA fiber analysis, to identify a key role for human RECQ1 helicase in replication fork restart after TOP1 inhibition, not shared by other human RecQ proteins. We show that the poly(ADPribosyl)ation activity of PARP1 stabilizes forks in their regressed state by limiting their restart by RECQ1. These studies provide new mechanistic insights into the roles of RECQ1 and PARP in DNA replication and offer molecular perspectives to potentiate chemotherapeutic regimens based on TOP1 inhibition.
publishDate	2013
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3897332/
_version_	1612049425544249344

Human RECQ1 promotes restart of replication forks reversed by DNA topoisomerase I inhibition

Similar Items