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

Berti, Matteo and Chaudhuri, Arnab Ray and Thangavel, Saravanabhavan and Gomathinayagam, Shivasankari and Kenig, Sasa and Vujanovic, Marko and Odreman, Federico and Glatter, Timo and Graziano, Simona and Mendoza-Maldonado, Ramiro and Marino, Francesca and Lucic, Bojana and Biasin, Valentina and Gstaiger, Matthias and Aebersold, Ruedi and Sidorova, Julia M. and Monnat, Raymond J. and Lopes, Massimo and Vindigni, Alessandro. (2013) Human RECQ1 promotes restart of replication forks reversed by DNA topoisomerase I inhibition. Nature structural & molecular biology, 20. pp. 347-354.

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Official URL: http://edoc.unibas.ch/dok/A6094002

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Abstract

Topoisomerase I (TOP1) inhibitors are an important class of anticancer drugs. The cytotoxicity of TOP1 inhibitors can be modulated by replication fork reversal through a process that requires poly(ADP-ribose) polymerase (PARP) activity. Whether regressed forks can efficiently restart and what factors are required to restart fork progression after fork reversal are still unknown. We have combined biochemical and EM approaches with single-molecule DNA fiber analysis to identify a key role for human RECQ1 helicase in replication fork restart after TOP1 inhibition that is not shared by other human RecQ proteins. We show that the poly(ADP-ribosyl)ation activity of PARP1 stabilizes forks in the 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.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Services Biozentrum > Proteomics (Schmidt)
UniBasel Contributors:Glatter, Timo
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Nature Publ. Group
ISSN:1545-9993
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:08 Jul 2016 07:44
Deposited On:26 Apr 2013 06:54

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