The MRX complex plays multiple functions in resection of Yku- and Rif2-protected DNA ends.

The ends of both double-strand breaks (DSBs) and telomeres undergo tightly regulated 5' to 3' resection. Resection of DNA ends, which is specifically inhibited during the G1 cell cycle phase, requires the MRX complex, Sae2, Sgs1 and Exo1. Moreover, it is negatively regulated by the non-hom...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Diego Bonetti, Michela Clerici, Nicola Manfrini, Giovanna Lucchini, Maria Pia Longhese
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/db0027d7be4c4230a880f2385becbc25
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:db0027d7be4c4230a880f2385becbc25
record_format	dspace
spelling	oai:doaj.org-article:db0027d7be4c4230a880f2385becbc252021-11-18T07:02:13ZThe MRX complex plays multiple functions in resection of Yku- and Rif2-protected DNA ends.1932-620310.1371/journal.pone.0014142https://doaj.org/article/db0027d7be4c4230a880f2385becbc252010-11-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21152442/?tool=EBIhttps://doaj.org/toc/1932-6203The ends of both double-strand breaks (DSBs) and telomeres undergo tightly regulated 5' to 3' resection. Resection of DNA ends, which is specifically inhibited during the G1 cell cycle phase, requires the MRX complex, Sae2, Sgs1 and Exo1. Moreover, it is negatively regulated by the non-homologous end-joining component Yku and the telomeric protein Rif2. Here, we investigate the nuclease activities that are inhibited at DNA ends by Rif2 and Yku in G1 versus G2 by using an inducible short telomere assay. We show that, in the absence of the protective function of Rif2, resection in G1 depends primarily on MRX nuclease activity and Sae2, whereas Exo1 and Sgs1 bypass the requirement of MRX nuclease activity only if Yku is absent. In contrast, Yku-mediated inhibition is relieved in G2, where resection depends on Mre11 nuclease activity, Exo1 and, to a minor extent, Sgs1. Furthermore, Exo1 compensates for a defective MRX nuclease activity more efficiently in the absence than in the presence of Rif2, suggesting that Rif2 inhibits not only MRX but also Exo1. Notably, the presence of MRX, but not its nuclease activity, is required and sufficient to override Yku-mediated inhibition of Exo1 in G2, whereas it is required but not sufficient in G1. Finally, the integrity of MRX is also necessary to promote Exo1- and Sgs1-dependent resection, possibly by facilitating Exo1 and Sgs1 recruitment to DNA ends. Thus, resection of DNA ends that are protected by Yku and Rif2 involves multiple functions of the MRX complex that do not necessarily require its nuclease activity.Diego BonettiMichela ClericiNicola ManfriniGiovanna LucchiniMaria Pia LonghesePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 11, p e14142 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Diego Bonetti Michela Clerici Nicola Manfrini Giovanna Lucchini Maria Pia Longhese The MRX complex plays multiple functions in resection of Yku- and Rif2-protected DNA ends.
description	The ends of both double-strand breaks (DSBs) and telomeres undergo tightly regulated 5' to 3' resection. Resection of DNA ends, which is specifically inhibited during the G1 cell cycle phase, requires the MRX complex, Sae2, Sgs1 and Exo1. Moreover, it is negatively regulated by the non-homologous end-joining component Yku and the telomeric protein Rif2. Here, we investigate the nuclease activities that are inhibited at DNA ends by Rif2 and Yku in G1 versus G2 by using an inducible short telomere assay. We show that, in the absence of the protective function of Rif2, resection in G1 depends primarily on MRX nuclease activity and Sae2, whereas Exo1 and Sgs1 bypass the requirement of MRX nuclease activity only if Yku is absent. In contrast, Yku-mediated inhibition is relieved in G2, where resection depends on Mre11 nuclease activity, Exo1 and, to a minor extent, Sgs1. Furthermore, Exo1 compensates for a defective MRX nuclease activity more efficiently in the absence than in the presence of Rif2, suggesting that Rif2 inhibits not only MRX but also Exo1. Notably, the presence of MRX, but not its nuclease activity, is required and sufficient to override Yku-mediated inhibition of Exo1 in G2, whereas it is required but not sufficient in G1. Finally, the integrity of MRX is also necessary to promote Exo1- and Sgs1-dependent resection, possibly by facilitating Exo1 and Sgs1 recruitment to DNA ends. Thus, resection of DNA ends that are protected by Yku and Rif2 involves multiple functions of the MRX complex that do not necessarily require its nuclease activity.
format	article
author	Diego Bonetti Michela Clerici Nicola Manfrini Giovanna Lucchini Maria Pia Longhese
author_facet	Diego Bonetti Michela Clerici Nicola Manfrini Giovanna Lucchini Maria Pia Longhese
author_sort	Diego Bonetti
title	The MRX complex plays multiple functions in resection of Yku- and Rif2-protected DNA ends.
title_short	The MRX complex plays multiple functions in resection of Yku- and Rif2-protected DNA ends.
title_full	The MRX complex plays multiple functions in resection of Yku- and Rif2-protected DNA ends.
title_fullStr	The MRX complex plays multiple functions in resection of Yku- and Rif2-protected DNA ends.
title_full_unstemmed	The MRX complex plays multiple functions in resection of Yku- and Rif2-protected DNA ends.
title_sort	mrx complex plays multiple functions in resection of yku- and rif2-protected dna ends.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/db0027d7be4c4230a880f2385becbc25
work_keys_str_mv	AT diegobonetti themrxcomplexplaysmultiplefunctionsinresectionofykuandrif2protecteddnaends AT michelaclerici themrxcomplexplaysmultiplefunctionsinresectionofykuandrif2protecteddnaends AT nicolamanfrini themrxcomplexplaysmultiplefunctionsinresectionofykuandrif2protecteddnaends AT giovannalucchini themrxcomplexplaysmultiplefunctionsinresectionofykuandrif2protecteddnaends AT mariapialonghese themrxcomplexplaysmultiplefunctionsinresectionofykuandrif2protecteddnaends AT diegobonetti mrxcomplexplaysmultiplefunctionsinresectionofykuandrif2protecteddnaends AT michelaclerici mrxcomplexplaysmultiplefunctionsinresectionofykuandrif2protecteddnaends AT nicolamanfrini mrxcomplexplaysmultiplefunctionsinresectionofykuandrif2protecteddnaends AT giovannalucchini mrxcomplexplaysmultiplefunctionsinresectionofykuandrif2protecteddnaends AT mariapialonghese mrxcomplexplaysmultiplefunctionsinresectionofykuandrif2protecteddnaends
_version_	1718424073629859840

The MRX complex plays multiple functions in resection of Yku- and Rif2-protected DNA ends.

Ejemplares similares