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Genetic and functional interactions between Mus81–Mms4 and Rad27

The two endonucleases, Rad27 (yeast Fen1) and Dna2, jointly participate in the processing of Okazaki fragments in yeasts. Mus81–Mms4 is a structure-specific endonuclease that can resolve stalled replication forks as well as toxic recombination intermediates. In this study, we show that Mus81–Mms4 ca...

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Autores principales: Kang, Min-Jung, Lee, Chul-Hwan, Kang, Young-Hoon, Cho, Il-Taeg, Nguyen, Tuan Anh, Seo, Yeon-Soo
Formato: Texto
Lenguaje:English
Publicado: Oxford University Press 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2995070/
https://www.ncbi.nlm.nih.gov/pubmed/20660481
http://dx.doi.org/10.1093/nar/gkq651
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author Kang, Min-Jung
Lee, Chul-Hwan
Kang, Young-Hoon
Cho, Il-Taeg
Nguyen, Tuan Anh
Seo, Yeon-Soo
author_facet Kang, Min-Jung
Lee, Chul-Hwan
Kang, Young-Hoon
Cho, Il-Taeg
Nguyen, Tuan Anh
Seo, Yeon-Soo
author_sort Kang, Min-Jung
collection PubMed
description The two endonucleases, Rad27 (yeast Fen1) and Dna2, jointly participate in the processing of Okazaki fragments in yeasts. Mus81–Mms4 is a structure-specific endonuclease that can resolve stalled replication forks as well as toxic recombination intermediates. In this study, we show that Mus81–Mms4 can suppress dna2 mutational defects by virtue of its functional and physical interaction with Rad27. Mus81–Mms4 stimulated Rad27 activity significantly, accounting for its ability to restore the growth defects caused by the dna2 mutation. Interestingly, Rad27 stimulated the rate of Mus81–Mms4 catalyzed cleavage of various substrates, including regressed replication fork substrates. The ability of Rad27 to stimulate Mus81–Mms4 did not depend on the catalytic activity of Rad27, but required the C-terminal 64 amino acid fragment of Rad27. This indicates that the stimulation was mediated by a specific protein–protein interaction between the two proteins. Our in vitro data indicate that Mus81–Mms4 and Rad27 act together during DNA replication and resolve various structures that can impede normal DNA replication. This conclusion was further strengthened by the fact that rad27 mus81 or rad27 mms4 double mutants were synergistically lethal. We discuss the significance of the interactions between Rad27, Dna2 and Mus81–Mms4 in context of DNA replication.
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spelling pubmed-29950702010-12-01 Genetic and functional interactions between Mus81–Mms4 and Rad27 Kang, Min-Jung Lee, Chul-Hwan Kang, Young-Hoon Cho, Il-Taeg Nguyen, Tuan Anh Seo, Yeon-Soo Nucleic Acids Res Nucleic Acid Enzymes The two endonucleases, Rad27 (yeast Fen1) and Dna2, jointly participate in the processing of Okazaki fragments in yeasts. Mus81–Mms4 is a structure-specific endonuclease that can resolve stalled replication forks as well as toxic recombination intermediates. In this study, we show that Mus81–Mms4 can suppress dna2 mutational defects by virtue of its functional and physical interaction with Rad27. Mus81–Mms4 stimulated Rad27 activity significantly, accounting for its ability to restore the growth defects caused by the dna2 mutation. Interestingly, Rad27 stimulated the rate of Mus81–Mms4 catalyzed cleavage of various substrates, including regressed replication fork substrates. The ability of Rad27 to stimulate Mus81–Mms4 did not depend on the catalytic activity of Rad27, but required the C-terminal 64 amino acid fragment of Rad27. This indicates that the stimulation was mediated by a specific protein–protein interaction between the two proteins. Our in vitro data indicate that Mus81–Mms4 and Rad27 act together during DNA replication and resolve various structures that can impede normal DNA replication. This conclusion was further strengthened by the fact that rad27 mus81 or rad27 mms4 double mutants were synergistically lethal. We discuss the significance of the interactions between Rad27, Dna2 and Mus81–Mms4 in context of DNA replication. Oxford University Press 2010-11 2010-07-25 /pmc/articles/PMC2995070/ /pubmed/20660481 http://dx.doi.org/10.1093/nar/gkq651 Text en © The Author(s) 2010. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/2.5 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Nucleic Acid Enzymes
Kang, Min-Jung
Lee, Chul-Hwan
Kang, Young-Hoon
Cho, Il-Taeg
Nguyen, Tuan Anh
Seo, Yeon-Soo
Genetic and functional interactions between Mus81–Mms4 and Rad27
title Genetic and functional interactions between Mus81–Mms4 and Rad27
title_full Genetic and functional interactions between Mus81–Mms4 and Rad27
title_fullStr Genetic and functional interactions between Mus81–Mms4 and Rad27
title_full_unstemmed Genetic and functional interactions between Mus81–Mms4 and Rad27
title_short Genetic and functional interactions between Mus81–Mms4 and Rad27
title_sort genetic and functional interactions between mus81–mms4 and rad27
topic Nucleic Acid Enzymes
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2995070/
https://www.ncbi.nlm.nih.gov/pubmed/20660481
http://dx.doi.org/10.1093/nar/gkq651
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