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Smc5/6-mediated regulation of replication progression contributes to chromosome assembly during mitosis in human cells

The structural maintenance of chromosomes (SMC) proteins constitute the core of critical complexes involved in structural organization of chromosomes. In yeast, the Smc5/6 complex is known to mediate repair of DNA breaks and replication of repetitive genomic regions, including ribosomal DNA loci and...

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Autores principales: Gallego-Paez, Lina Marcela, Tanaka, Hiroshi, Bando, Masashige, Takahashi, Motoko, Nozaki, Naohito, Nakato, Ryuichiro, Shirahige, Katsuhiko, Hirota, Toru
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3890350/
https://www.ncbi.nlm.nih.gov/pubmed/24258023
http://dx.doi.org/10.1091/mbc.E13-01-0020
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author Gallego-Paez, Lina Marcela
Tanaka, Hiroshi
Bando, Masashige
Takahashi, Motoko
Nozaki, Naohito
Nakato, Ryuichiro
Shirahige, Katsuhiko
Hirota, Toru
author_facet Gallego-Paez, Lina Marcela
Tanaka, Hiroshi
Bando, Masashige
Takahashi, Motoko
Nozaki, Naohito
Nakato, Ryuichiro
Shirahige, Katsuhiko
Hirota, Toru
author_sort Gallego-Paez, Lina Marcela
collection PubMed
description The structural maintenance of chromosomes (SMC) proteins constitute the core of critical complexes involved in structural organization of chromosomes. In yeast, the Smc5/6 complex is known to mediate repair of DNA breaks and replication of repetitive genomic regions, including ribosomal DNA loci and telomeres. In mammalian cells, which have diverse genome structure and scale from yeast, the Smc5/6 complex has also been implicated in DNA damage response, but its further function in unchallenged conditions remains elusive. In this study, we addressed the behavior and function of Smc5/6 during the cell cycle. Chromatin fractionation, immunofluorescence, and live-cell imaging analyses indicated that Smc5/6 associates with chromatin during interphase but largely dissociates from chromosomes when they condense in mitosis. Depletion of Smc5 and Smc6 resulted in aberrant mitotic chromosome phenotypes that were accompanied by the abnormal distribution of topoisomerase IIα (topo IIα) and condensins and by chromosome segregation errors. Importantly, interphase chromatin structure indicated by the premature chromosome condensation assay suggested that Smc5/6 is required for the on-time progression of DNA replication and subsequent binding of topo IIα on replicated chromatids. These results indicate an essential role of the Smc5/6 complex in processing DNA replication, which becomes indispensable for proper sister chromatid assembly in mitosis.
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spelling pubmed-38903502014-03-30 Smc5/6-mediated regulation of replication progression contributes to chromosome assembly during mitosis in human cells Gallego-Paez, Lina Marcela Tanaka, Hiroshi Bando, Masashige Takahashi, Motoko Nozaki, Naohito Nakato, Ryuichiro Shirahige, Katsuhiko Hirota, Toru Mol Biol Cell Articles The structural maintenance of chromosomes (SMC) proteins constitute the core of critical complexes involved in structural organization of chromosomes. In yeast, the Smc5/6 complex is known to mediate repair of DNA breaks and replication of repetitive genomic regions, including ribosomal DNA loci and telomeres. In mammalian cells, which have diverse genome structure and scale from yeast, the Smc5/6 complex has also been implicated in DNA damage response, but its further function in unchallenged conditions remains elusive. In this study, we addressed the behavior and function of Smc5/6 during the cell cycle. Chromatin fractionation, immunofluorescence, and live-cell imaging analyses indicated that Smc5/6 associates with chromatin during interphase but largely dissociates from chromosomes when they condense in mitosis. Depletion of Smc5 and Smc6 resulted in aberrant mitotic chromosome phenotypes that were accompanied by the abnormal distribution of topoisomerase IIα (topo IIα) and condensins and by chromosome segregation errors. Importantly, interphase chromatin structure indicated by the premature chromosome condensation assay suggested that Smc5/6 is required for the on-time progression of DNA replication and subsequent binding of topo IIα on replicated chromatids. These results indicate an essential role of the Smc5/6 complex in processing DNA replication, which becomes indispensable for proper sister chromatid assembly in mitosis. The American Society for Cell Biology 2014-01-15 /pmc/articles/PMC3890350/ /pubmed/24258023 http://dx.doi.org/10.1091/mbc.E13-01-0020 Text en © 2014 Gallego-Paez et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology.
spellingShingle Articles
Gallego-Paez, Lina Marcela
Tanaka, Hiroshi
Bando, Masashige
Takahashi, Motoko
Nozaki, Naohito
Nakato, Ryuichiro
Shirahige, Katsuhiko
Hirota, Toru
Smc5/6-mediated regulation of replication progression contributes to chromosome assembly during mitosis in human cells
title Smc5/6-mediated regulation of replication progression contributes to chromosome assembly during mitosis in human cells
title_full Smc5/6-mediated regulation of replication progression contributes to chromosome assembly during mitosis in human cells
title_fullStr Smc5/6-mediated regulation of replication progression contributes to chromosome assembly during mitosis in human cells
title_full_unstemmed Smc5/6-mediated regulation of replication progression contributes to chromosome assembly during mitosis in human cells
title_short Smc5/6-mediated regulation of replication progression contributes to chromosome assembly during mitosis in human cells
title_sort smc5/6-mediated regulation of replication progression contributes to chromosome assembly during mitosis in human cells
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3890350/
https://www.ncbi.nlm.nih.gov/pubmed/24258023
http://dx.doi.org/10.1091/mbc.E13-01-0020
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