Searching for DNA Damage: Insights From Single Molecule Analysis

DNA is under constant threat of damage from a variety of chemical and physical insults, such as ultraviolet rays produced by sunlight and reactive oxygen species produced during respiration or inflammation. Because damaged DNA, if not repaired, can lead to mutations or cell death, multiple DNA repai...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Matthew A. Schaich, Bennett Van Houten
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	single molecule fluorescence microscopy DNA tightrope nucleotide excision repair base excision repair DNA damage Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/272bd76ac4f84daebaf4e6fd2233bedf
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:272bd76ac4f84daebaf4e6fd2233bedf
record_format	dspace
spelling	oai:doaj.org-article:272bd76ac4f84daebaf4e6fd2233bedf2021-11-05T08:22:42ZSearching for DNA Damage: Insights From Single Molecule Analysis2296-889X10.3389/fmolb.2021.772877https://doaj.org/article/272bd76ac4f84daebaf4e6fd2233bedf2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fmolb.2021.772877/fullhttps://doaj.org/toc/2296-889XDNA is under constant threat of damage from a variety of chemical and physical insults, such as ultraviolet rays produced by sunlight and reactive oxygen species produced during respiration or inflammation. Because damaged DNA, if not repaired, can lead to mutations or cell death, multiple DNA repair pathways have evolved to maintain genome stability. Two repair pathways, nucleotide excision repair (NER) and base excision repair (BER), must sift through large segments of nondamaged nucleotides to detect and remove rare base modifications. Many BER and NER proteins share a common base-flipping mechanism for the detection of modified bases. However, the exact mechanisms by which these repair proteins detect their damaged substrates in the context of cellular chromatin remains unclear. The latest generation of single-molecule techniques, including the DNA tightrope assay, atomic force microscopy, and real-time imaging in cells, now allows for nearly direct visualization of the damage search and detection processes. This review describes several mechanistic commonalities for damage detection that were discovered with these techniques, including a combination of 3-dimensional and linear diffusion for surveying damaged sites within long stretches of DNA. We also discuss important findings that DNA repair proteins within and between pathways cooperate to detect damage. Finally, future technical developments and single-molecule studies are described which will contribute to the growing mechanistic understanding of DNA damage detection.Matthew A. SchaichMatthew A. SchaichBennett Van HoutenBennett Van HoutenBennett Van HoutenFrontiers Media S.A.articlesingle molecule fluorescence microscopyDNA tightropenucleotide excision repairbase excision repairDNA damageBiology (General)QH301-705.5ENFrontiers in Molecular Biosciences, Vol 8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	single molecule fluorescence microscopy DNA tightrope nucleotide excision repair base excision repair DNA damage Biology (General) QH301-705.5
spellingShingle	single molecule fluorescence microscopy DNA tightrope nucleotide excision repair base excision repair DNA damage Biology (General) QH301-705.5 Matthew A. Schaich Matthew A. Schaich Bennett Van Houten Bennett Van Houten Bennett Van Houten Searching for DNA Damage: Insights From Single Molecule Analysis
description	DNA is under constant threat of damage from a variety of chemical and physical insults, such as ultraviolet rays produced by sunlight and reactive oxygen species produced during respiration or inflammation. Because damaged DNA, if not repaired, can lead to mutations or cell death, multiple DNA repair pathways have evolved to maintain genome stability. Two repair pathways, nucleotide excision repair (NER) and base excision repair (BER), must sift through large segments of nondamaged nucleotides to detect and remove rare base modifications. Many BER and NER proteins share a common base-flipping mechanism for the detection of modified bases. However, the exact mechanisms by which these repair proteins detect their damaged substrates in the context of cellular chromatin remains unclear. The latest generation of single-molecule techniques, including the DNA tightrope assay, atomic force microscopy, and real-time imaging in cells, now allows for nearly direct visualization of the damage search and detection processes. This review describes several mechanistic commonalities for damage detection that were discovered with these techniques, including a combination of 3-dimensional and linear diffusion for surveying damaged sites within long stretches of DNA. We also discuss important findings that DNA repair proteins within and between pathways cooperate to detect damage. Finally, future technical developments and single-molecule studies are described which will contribute to the growing mechanistic understanding of DNA damage detection.
format	article
author	Matthew A. Schaich Matthew A. Schaich Bennett Van Houten Bennett Van Houten Bennett Van Houten
author_facet	Matthew A. Schaich Matthew A. Schaich Bennett Van Houten Bennett Van Houten Bennett Van Houten
author_sort	Matthew A. Schaich
title	Searching for DNA Damage: Insights From Single Molecule Analysis
title_short	Searching for DNA Damage: Insights From Single Molecule Analysis
title_full	Searching for DNA Damage: Insights From Single Molecule Analysis
title_fullStr	Searching for DNA Damage: Insights From Single Molecule Analysis
title_full_unstemmed	Searching for DNA Damage: Insights From Single Molecule Analysis
title_sort	searching for dna damage: insights from single molecule analysis
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/272bd76ac4f84daebaf4e6fd2233bedf
work_keys_str_mv	AT matthewaschaich searchingfordnadamageinsightsfromsinglemoleculeanalysis AT matthewaschaich searchingfordnadamageinsightsfromsinglemoleculeanalysis AT bennettvanhouten searchingfordnadamageinsightsfromsinglemoleculeanalysis AT bennettvanhouten searchingfordnadamageinsightsfromsinglemoleculeanalysis AT bennettvanhouten searchingfordnadamageinsightsfromsinglemoleculeanalysis
_version_	1718444456500264960

Searching for DNA Damage: Insights From Single Molecule Analysis

Ejemplares similares