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Biology before the SOS Response—DNA Damage Mechanisms at Chromosome Fragile Sites

The Escherichia coli SOS response to DNA damage, discovered and conceptualized by Evelyn Witkin and Miroslav Radman, is the prototypic DNA-damage stress response that upregulates proteins of DNA protection and repair, a radical idea when formulated in the late 1960s and early 1970s. SOS-like respons...

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Autores principales: Fitzgerald, Devon M., Rosenberg, Susan M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8465572/
https://www.ncbi.nlm.nih.gov/pubmed/34571923
http://dx.doi.org/10.3390/cells10092275
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author Fitzgerald, Devon M.
Rosenberg, Susan M.
author_facet Fitzgerald, Devon M.
Rosenberg, Susan M.
author_sort Fitzgerald, Devon M.
collection PubMed
description The Escherichia coli SOS response to DNA damage, discovered and conceptualized by Evelyn Witkin and Miroslav Radman, is the prototypic DNA-damage stress response that upregulates proteins of DNA protection and repair, a radical idea when formulated in the late 1960s and early 1970s. SOS-like responses are now described across the tree of life, and similar mechanisms of DNA-damage tolerance and repair underlie the genome instability that drives human cancer and aging. The DNA damage that precedes damage responses constitutes upstream threats to genome integrity and arises mostly from endogenous biology. Radman’s vision and work on SOS, mismatch repair, and their regulation of genome and species evolution, were extrapolated directly from bacteria to humans, at a conceptual level, by Radman, then many others. We follow his lead in exploring bacterial molecular genomic mechanisms to illuminate universal biology, including in human disease, and focus here on some events upstream of SOS: the origins of DNA damage, specifically at chromosome fragile sites, and the engineered proteins that allow us to identify mechanisms. Two fragility mechanisms dominate: one at replication barriers and another associated with the decatenation of sister chromosomes following replication. DNA structures in E. coli, additionally, suggest new interpretations of pathways in cancer evolution, and that Holliday junctions may be universal molecular markers of chromosome fragility.
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spelling pubmed-84655722021-09-27 Biology before the SOS Response—DNA Damage Mechanisms at Chromosome Fragile Sites Fitzgerald, Devon M. Rosenberg, Susan M. Cells Review The Escherichia coli SOS response to DNA damage, discovered and conceptualized by Evelyn Witkin and Miroslav Radman, is the prototypic DNA-damage stress response that upregulates proteins of DNA protection and repair, a radical idea when formulated in the late 1960s and early 1970s. SOS-like responses are now described across the tree of life, and similar mechanisms of DNA-damage tolerance and repair underlie the genome instability that drives human cancer and aging. The DNA damage that precedes damage responses constitutes upstream threats to genome integrity and arises mostly from endogenous biology. Radman’s vision and work on SOS, mismatch repair, and their regulation of genome and species evolution, were extrapolated directly from bacteria to humans, at a conceptual level, by Radman, then many others. We follow his lead in exploring bacterial molecular genomic mechanisms to illuminate universal biology, including in human disease, and focus here on some events upstream of SOS: the origins of DNA damage, specifically at chromosome fragile sites, and the engineered proteins that allow us to identify mechanisms. Two fragility mechanisms dominate: one at replication barriers and another associated with the decatenation of sister chromosomes following replication. DNA structures in E. coli, additionally, suggest new interpretations of pathways in cancer evolution, and that Holliday junctions may be universal molecular markers of chromosome fragility. MDPI 2021-09-01 /pmc/articles/PMC8465572/ /pubmed/34571923 http://dx.doi.org/10.3390/cells10092275 Text en © 2021 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 Review
Fitzgerald, Devon M.
Rosenberg, Susan M.
Biology before the SOS Response—DNA Damage Mechanisms at Chromosome Fragile Sites
title Biology before the SOS Response—DNA Damage Mechanisms at Chromosome Fragile Sites
title_full Biology before the SOS Response—DNA Damage Mechanisms at Chromosome Fragile Sites
title_fullStr Biology before the SOS Response—DNA Damage Mechanisms at Chromosome Fragile Sites
title_full_unstemmed Biology before the SOS Response—DNA Damage Mechanisms at Chromosome Fragile Sites
title_short Biology before the SOS Response—DNA Damage Mechanisms at Chromosome Fragile Sites
title_sort biology before the sos response—dna damage mechanisms at chromosome fragile sites
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8465572/
https://www.ncbi.nlm.nih.gov/pubmed/34571923
http://dx.doi.org/10.3390/cells10092275
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