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Mini-chromosome maintenance complexes form a filament to remodel DNA structure and topology

Deregulation of mini-chromosome maintenance (MCM) proteins is associated with genomic instability and cancer. MCM complexes are recruited to replication origins for genome duplication. Paradoxically, MCM proteins are in excess than the number of origins and are associated with chromatin regions away...

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Autores principales: Slaymaker, Ian M., Fu, Yang, Toso, Daniel B., Ranatunga, Nimna, Brewster, Aaron, Forsburg, Susan L., Zhou, Z. Hong, Chen, Xiaojiang S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3597688/
https://www.ncbi.nlm.nih.gov/pubmed/23361460
http://dx.doi.org/10.1093/nar/gkt022
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author Slaymaker, Ian M.
Fu, Yang
Toso, Daniel B.
Ranatunga, Nimna
Brewster, Aaron
Forsburg, Susan L.
Zhou, Z. Hong
Chen, Xiaojiang S.
author_facet Slaymaker, Ian M.
Fu, Yang
Toso, Daniel B.
Ranatunga, Nimna
Brewster, Aaron
Forsburg, Susan L.
Zhou, Z. Hong
Chen, Xiaojiang S.
author_sort Slaymaker, Ian M.
collection PubMed
description Deregulation of mini-chromosome maintenance (MCM) proteins is associated with genomic instability and cancer. MCM complexes are recruited to replication origins for genome duplication. Paradoxically, MCM proteins are in excess than the number of origins and are associated with chromatin regions away from the origins during G1 and S phases. Here, we report an unusually wide left-handed filament structure for an archaeal MCM, as determined by X-ray and electron microscopy. The crystal structure reveals that an α-helix bundle formed between two neighboring subunits plays a critical role in filament formation. The filament has a remarkably strong electro-positive surface spiraling along the inner filament channel for DNA binding. We show that this MCM filament binding to DNA causes dramatic DNA topology change. This newly identified function of MCM to change DNA topology may imply a wider functional role for MCM in DNA metabolisms beyond helicase function. Finally, using yeast genetics, we show that the inter-subunit interactions, important for MCM filament formation, play a role for cell growth and survival.
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spelling pubmed-35976882013-03-15 Mini-chromosome maintenance complexes form a filament to remodel DNA structure and topology Slaymaker, Ian M. Fu, Yang Toso, Daniel B. Ranatunga, Nimna Brewster, Aaron Forsburg, Susan L. Zhou, Z. Hong Chen, Xiaojiang S. Nucleic Acids Res Structural Biology Deregulation of mini-chromosome maintenance (MCM) proteins is associated with genomic instability and cancer. MCM complexes are recruited to replication origins for genome duplication. Paradoxically, MCM proteins are in excess than the number of origins and are associated with chromatin regions away from the origins during G1 and S phases. Here, we report an unusually wide left-handed filament structure for an archaeal MCM, as determined by X-ray and electron microscopy. The crystal structure reveals that an α-helix bundle formed between two neighboring subunits plays a critical role in filament formation. The filament has a remarkably strong electro-positive surface spiraling along the inner filament channel for DNA binding. We show that this MCM filament binding to DNA causes dramatic DNA topology change. This newly identified function of MCM to change DNA topology may imply a wider functional role for MCM in DNA metabolisms beyond helicase function. Finally, using yeast genetics, we show that the inter-subunit interactions, important for MCM filament formation, play a role for cell growth and survival. Oxford University Press 2013-03 2013-01-29 /pmc/articles/PMC3597688/ /pubmed/23361460 http://dx.doi.org/10.1093/nar/gkt022 Text en Published by Oxford University Press 2013. http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Structural Biology
Slaymaker, Ian M.
Fu, Yang
Toso, Daniel B.
Ranatunga, Nimna
Brewster, Aaron
Forsburg, Susan L.
Zhou, Z. Hong
Chen, Xiaojiang S.
Mini-chromosome maintenance complexes form a filament to remodel DNA structure and topology
title Mini-chromosome maintenance complexes form a filament to remodel DNA structure and topology
title_full Mini-chromosome maintenance complexes form a filament to remodel DNA structure and topology
title_fullStr Mini-chromosome maintenance complexes form a filament to remodel DNA structure and topology
title_full_unstemmed Mini-chromosome maintenance complexes form a filament to remodel DNA structure and topology
title_short Mini-chromosome maintenance complexes form a filament to remodel DNA structure and topology
title_sort mini-chromosome maintenance complexes form a filament to remodel dna structure and topology
topic Structural Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3597688/
https://www.ncbi.nlm.nih.gov/pubmed/23361460
http://dx.doi.org/10.1093/nar/gkt022
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