Cargando…
Two Distinct Modes of DNA Binding by an MCM Helicase Enable DNA Translocation
A six-subunit ATPase ring forms the central hub of the replication forks in all domains of life. This ring performs a helicase function to separate the two complementary DNA strands to be replicated and drives the replication machinery along the DNA. Disruption of this helicase/ATPase ring is associ...
Autores principales: | , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9735655/ https://www.ncbi.nlm.nih.gov/pubmed/36499022 http://dx.doi.org/10.3390/ijms232314678 |
_version_ | 1784846823882489856 |
---|---|
author | Meagher, Martin Myasnikov, Alexander Enemark, Eric J. |
author_facet | Meagher, Martin Myasnikov, Alexander Enemark, Eric J. |
author_sort | Meagher, Martin |
collection | PubMed |
description | A six-subunit ATPase ring forms the central hub of the replication forks in all domains of life. This ring performs a helicase function to separate the two complementary DNA strands to be replicated and drives the replication machinery along the DNA. Disruption of this helicase/ATPase ring is associated with genetic instability and diseases such as cancer. The helicase/ATPase rings of eukaryotes and archaea consist of six minichromosome maintenance (MCM) proteins. Prior structural studies have shown that MCM rings bind one encircled strand of DNA in a spiral staircase, suggesting that the ring pulls this strand of DNA through its central pore in a hand-over-hand mechanism where the subunit at the bottom of the staircase dissociates from DNA and re-binds DNA one step above the staircase. With high-resolution cryo-EM, we show that the MCM ring of the archaeal organism Saccharolobus solfataricus binds an encircled DNA strand in two different modes with different numbers of subunits engaged to DNA, illustrating a plausible mechanism for the alternating steps of DNA dissociation and re-association that occur during DNA translocation. |
format | Online Article Text |
id | pubmed-9735655 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-97356552022-12-11 Two Distinct Modes of DNA Binding by an MCM Helicase Enable DNA Translocation Meagher, Martin Myasnikov, Alexander Enemark, Eric J. Int J Mol Sci Article A six-subunit ATPase ring forms the central hub of the replication forks in all domains of life. This ring performs a helicase function to separate the two complementary DNA strands to be replicated and drives the replication machinery along the DNA. Disruption of this helicase/ATPase ring is associated with genetic instability and diseases such as cancer. The helicase/ATPase rings of eukaryotes and archaea consist of six minichromosome maintenance (MCM) proteins. Prior structural studies have shown that MCM rings bind one encircled strand of DNA in a spiral staircase, suggesting that the ring pulls this strand of DNA through its central pore in a hand-over-hand mechanism where the subunit at the bottom of the staircase dissociates from DNA and re-binds DNA one step above the staircase. With high-resolution cryo-EM, we show that the MCM ring of the archaeal organism Saccharolobus solfataricus binds an encircled DNA strand in two different modes with different numbers of subunits engaged to DNA, illustrating a plausible mechanism for the alternating steps of DNA dissociation and re-association that occur during DNA translocation. MDPI 2022-11-24 /pmc/articles/PMC9735655/ /pubmed/36499022 http://dx.doi.org/10.3390/ijms232314678 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Meagher, Martin Myasnikov, Alexander Enemark, Eric J. Two Distinct Modes of DNA Binding by an MCM Helicase Enable DNA Translocation |
title | Two Distinct Modes of DNA Binding by an MCM Helicase Enable DNA Translocation |
title_full | Two Distinct Modes of DNA Binding by an MCM Helicase Enable DNA Translocation |
title_fullStr | Two Distinct Modes of DNA Binding by an MCM Helicase Enable DNA Translocation |
title_full_unstemmed | Two Distinct Modes of DNA Binding by an MCM Helicase Enable DNA Translocation |
title_short | Two Distinct Modes of DNA Binding by an MCM Helicase Enable DNA Translocation |
title_sort | two distinct modes of dna binding by an mcm helicase enable dna translocation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9735655/ https://www.ncbi.nlm.nih.gov/pubmed/36499022 http://dx.doi.org/10.3390/ijms232314678 |
work_keys_str_mv | AT meaghermartin twodistinctmodesofdnabindingbyanmcmhelicaseenablednatranslocation AT myasnikovalexander twodistinctmodesofdnabindingbyanmcmhelicaseenablednatranslocation AT enemarkericj twodistinctmodesofdnabindingbyanmcmhelicaseenablednatranslocation |