Cargando…

A chromatin scaffold for DNA damage recognition: how histone methyltransferases prime nucleosomes for repair of ultraviolet light-induced lesions

The excision of mutagenic DNA adducts by the nucleotide excision repair (NER) pathway is essential for genome stability, which is key to avoiding genetic diseases, premature aging, cancer and neurologic disorders. Due to the need to process an extraordinarily high damage density embedded in the nucl...

Descripción completa

Detalles Bibliográficos
Autores principales: Gsell, Corina, Richly, Holger, Coin, Frédéric, Naegeli, Hanspeter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7038933/
https://www.ncbi.nlm.nih.gov/pubmed/31930303
http://dx.doi.org/10.1093/nar/gkz1229
_version_ 1783500731772305408
author Gsell, Corina
Richly, Holger
Coin, Frédéric
Naegeli, Hanspeter
author_facet Gsell, Corina
Richly, Holger
Coin, Frédéric
Naegeli, Hanspeter
author_sort Gsell, Corina
collection PubMed
description The excision of mutagenic DNA adducts by the nucleotide excision repair (NER) pathway is essential for genome stability, which is key to avoiding genetic diseases, premature aging, cancer and neurologic disorders. Due to the need to process an extraordinarily high damage density embedded in the nucleosome landscape of chromatin, NER activity provides a unique functional caliper to understand how histone modifiers modulate DNA damage responses. At least three distinct lysine methyltransferases (KMTs) targeting histones have been shown to facilitate the detection of ultraviolet (UV) light-induced DNA lesions in the difficult to access DNA wrapped around histones in nucleosomes. By methylating core histones, these KMTs generate docking sites for DNA damage recognition factors before the chromatin structure is ultimately relaxed and the offending lesions are effectively excised. In view of their function in priming nucleosomes for DNA repair, mutations of genes coding for these KMTs are expected to cause the accumulation of DNA damage promoting cancer and other chronic diseases. Research on the question of how KMTs modulate DNA repair might pave the way to the development of pharmacologic agents for novel therapeutic strategies.
format Online
Article
Text
id pubmed-7038933
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Oxford University Press
record_format MEDLINE/PubMed
spelling pubmed-70389332020-03-02 A chromatin scaffold for DNA damage recognition: how histone methyltransferases prime nucleosomes for repair of ultraviolet light-induced lesions Gsell, Corina Richly, Holger Coin, Frédéric Naegeli, Hanspeter Nucleic Acids Res Survey and Summary The excision of mutagenic DNA adducts by the nucleotide excision repair (NER) pathway is essential for genome stability, which is key to avoiding genetic diseases, premature aging, cancer and neurologic disorders. Due to the need to process an extraordinarily high damage density embedded in the nucleosome landscape of chromatin, NER activity provides a unique functional caliper to understand how histone modifiers modulate DNA damage responses. At least three distinct lysine methyltransferases (KMTs) targeting histones have been shown to facilitate the detection of ultraviolet (UV) light-induced DNA lesions in the difficult to access DNA wrapped around histones in nucleosomes. By methylating core histones, these KMTs generate docking sites for DNA damage recognition factors before the chromatin structure is ultimately relaxed and the offending lesions are effectively excised. In view of their function in priming nucleosomes for DNA repair, mutations of genes coding for these KMTs are expected to cause the accumulation of DNA damage promoting cancer and other chronic diseases. Research on the question of how KMTs modulate DNA repair might pave the way to the development of pharmacologic agents for novel therapeutic strategies. Oxford University Press 2020-02-28 2020-01-13 /pmc/articles/PMC7038933/ /pubmed/31930303 http://dx.doi.org/10.1093/nar/gkz1229 Text en © The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Survey and Summary
Gsell, Corina
Richly, Holger
Coin, Frédéric
Naegeli, Hanspeter
A chromatin scaffold for DNA damage recognition: how histone methyltransferases prime nucleosomes for repair of ultraviolet light-induced lesions
title A chromatin scaffold for DNA damage recognition: how histone methyltransferases prime nucleosomes for repair of ultraviolet light-induced lesions
title_full A chromatin scaffold for DNA damage recognition: how histone methyltransferases prime nucleosomes for repair of ultraviolet light-induced lesions
title_fullStr A chromatin scaffold for DNA damage recognition: how histone methyltransferases prime nucleosomes for repair of ultraviolet light-induced lesions
title_full_unstemmed A chromatin scaffold for DNA damage recognition: how histone methyltransferases prime nucleosomes for repair of ultraviolet light-induced lesions
title_short A chromatin scaffold for DNA damage recognition: how histone methyltransferases prime nucleosomes for repair of ultraviolet light-induced lesions
title_sort chromatin scaffold for dna damage recognition: how histone methyltransferases prime nucleosomes for repair of ultraviolet light-induced lesions
topic Survey and Summary
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7038933/
https://www.ncbi.nlm.nih.gov/pubmed/31930303
http://dx.doi.org/10.1093/nar/gkz1229
work_keys_str_mv AT gsellcorina achromatinscaffoldfordnadamagerecognitionhowhistonemethyltransferasesprimenucleosomesforrepairofultravioletlightinducedlesions
AT richlyholger achromatinscaffoldfordnadamagerecognitionhowhistonemethyltransferasesprimenucleosomesforrepairofultravioletlightinducedlesions
AT coinfrederic achromatinscaffoldfordnadamagerecognitionhowhistonemethyltransferasesprimenucleosomesforrepairofultravioletlightinducedlesions
AT naegelihanspeter achromatinscaffoldfordnadamagerecognitionhowhistonemethyltransferasesprimenucleosomesforrepairofultravioletlightinducedlesions
AT gsellcorina chromatinscaffoldfordnadamagerecognitionhowhistonemethyltransferasesprimenucleosomesforrepairofultravioletlightinducedlesions
AT richlyholger chromatinscaffoldfordnadamagerecognitionhowhistonemethyltransferasesprimenucleosomesforrepairofultravioletlightinducedlesions
AT coinfrederic chromatinscaffoldfordnadamagerecognitionhowhistonemethyltransferasesprimenucleosomesforrepairofultravioletlightinducedlesions
AT naegelihanspeter chromatinscaffoldfordnadamagerecognitionhowhistonemethyltransferasesprimenucleosomesforrepairofultravioletlightinducedlesions