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Spatial and temporal organization of RecA in the Escherichia coli DNA-damage response

The RecA protein orchestrates the cellular response to DNA damage via its multiple roles in the bacterial SOS response. Lack of tools that provide unambiguous access to the various RecA states within the cell have prevented understanding of the spatial and temporal changes in RecA structure/function...

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Autores principales: Ghodke, Harshad, Paudel, Bishnu P, Lewis, Jacob S, Jergic, Slobodan, Gopal, Kamya, Romero, Zachary J, Wood, Elizabeth A, Woodgate, Roger, Cox, Michael M, van Oijen, Antoine M
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6363387/
https://www.ncbi.nlm.nih.gov/pubmed/30717823
http://dx.doi.org/10.7554/eLife.42761
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author Ghodke, Harshad
Paudel, Bishnu P
Lewis, Jacob S
Jergic, Slobodan
Gopal, Kamya
Romero, Zachary J
Wood, Elizabeth A
Woodgate, Roger
Cox, Michael M
van Oijen, Antoine M
author_facet Ghodke, Harshad
Paudel, Bishnu P
Lewis, Jacob S
Jergic, Slobodan
Gopal, Kamya
Romero, Zachary J
Wood, Elizabeth A
Woodgate, Roger
Cox, Michael M
van Oijen, Antoine M
author_sort Ghodke, Harshad
collection PubMed
description The RecA protein orchestrates the cellular response to DNA damage via its multiple roles in the bacterial SOS response. Lack of tools that provide unambiguous access to the various RecA states within the cell have prevented understanding of the spatial and temporal changes in RecA structure/function that underlie control of the damage response. Here, we develop a monomeric C-terminal fragment of the λ repressor as a novel fluorescent probe that specifically interacts with RecA filaments on single-stranded DNA (RecA*). Single-molecule imaging techniques in live cells demonstrate that RecA is largely sequestered in storage structures during normal metabolism. Upon DNA damage, the storage structures dissolve and the cytosolic pool of RecA rapidly nucleates to form early SOS-signaling complexes, maturing into DNA-bound RecA bundles at later time points. Both before and after SOS induction, RecA* largely appears at locations distal from replisomes. Upon completion of repair, RecA storage structures reform.
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spelling pubmed-63633872019-02-06 Spatial and temporal organization of RecA in the Escherichia coli DNA-damage response Ghodke, Harshad Paudel, Bishnu P Lewis, Jacob S Jergic, Slobodan Gopal, Kamya Romero, Zachary J Wood, Elizabeth A Woodgate, Roger Cox, Michael M van Oijen, Antoine M eLife Physics of Living Systems The RecA protein orchestrates the cellular response to DNA damage via its multiple roles in the bacterial SOS response. Lack of tools that provide unambiguous access to the various RecA states within the cell have prevented understanding of the spatial and temporal changes in RecA structure/function that underlie control of the damage response. Here, we develop a monomeric C-terminal fragment of the λ repressor as a novel fluorescent probe that specifically interacts with RecA filaments on single-stranded DNA (RecA*). Single-molecule imaging techniques in live cells demonstrate that RecA is largely sequestered in storage structures during normal metabolism. Upon DNA damage, the storage structures dissolve and the cytosolic pool of RecA rapidly nucleates to form early SOS-signaling complexes, maturing into DNA-bound RecA bundles at later time points. Both before and after SOS induction, RecA* largely appears at locations distal from replisomes. Upon completion of repair, RecA storage structures reform. eLife Sciences Publications, Ltd 2019-02-05 /pmc/articles/PMC6363387/ /pubmed/30717823 http://dx.doi.org/10.7554/eLife.42761 Text en http://creativecommons.org/publicdomain/zero/1.0/ http://creativecommons.org/publicdomain/zero/1.0/This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication (http://creativecommons.org/publicdomain/zero/1.0/) .
spellingShingle Physics of Living Systems
Ghodke, Harshad
Paudel, Bishnu P
Lewis, Jacob S
Jergic, Slobodan
Gopal, Kamya
Romero, Zachary J
Wood, Elizabeth A
Woodgate, Roger
Cox, Michael M
van Oijen, Antoine M
Spatial and temporal organization of RecA in the Escherichia coli DNA-damage response
title Spatial and temporal organization of RecA in the Escherichia coli DNA-damage response
title_full Spatial and temporal organization of RecA in the Escherichia coli DNA-damage response
title_fullStr Spatial and temporal organization of RecA in the Escherichia coli DNA-damage response
title_full_unstemmed Spatial and temporal organization of RecA in the Escherichia coli DNA-damage response
title_short Spatial and temporal organization of RecA in the Escherichia coli DNA-damage response
title_sort spatial and temporal organization of reca in the escherichia coli dna-damage response
topic Physics of Living Systems
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6363387/
https://www.ncbi.nlm.nih.gov/pubmed/30717823
http://dx.doi.org/10.7554/eLife.42761
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