Cargando…

hSSB1 (NABP2/ OBFC2B) is required for the repair of 8-oxo-guanine by the hOGG1-mediated base excision repair pathway

The maintenance of genome stability is essential to prevent loss of genetic information and the development of diseases such as cancer. One of the most common forms of damage to the genetic code is the oxidation of DNA by reactive oxygen species (ROS), of which 8-oxo-7,8-dihydro-guanine (8-oxoG) is...

Descripción completa

Detalles Bibliográficos
Autores principales: Paquet, Nicolas, Adams, Mark N., Leong, Vincent, Ashton, Nicholas W., Touma, Christine, Gamsjaeger, Roland, Cubeddu, Liza, Beard, Sam, Burgess, Joshua T., Bolderson, Emma, O'Byrne, Ken J., Richard, Derek J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4605301/
https://www.ncbi.nlm.nih.gov/pubmed/26261212
http://dx.doi.org/10.1093/nar/gkv790
_version_ 1782395188666171392
author Paquet, Nicolas
Adams, Mark N.
Leong, Vincent
Ashton, Nicholas W.
Touma, Christine
Gamsjaeger, Roland
Cubeddu, Liza
Beard, Sam
Burgess, Joshua T.
Bolderson, Emma
O'Byrne, Ken J.
Richard, Derek J.
author_facet Paquet, Nicolas
Adams, Mark N.
Leong, Vincent
Ashton, Nicholas W.
Touma, Christine
Gamsjaeger, Roland
Cubeddu, Liza
Beard, Sam
Burgess, Joshua T.
Bolderson, Emma
O'Byrne, Ken J.
Richard, Derek J.
author_sort Paquet, Nicolas
collection PubMed
description The maintenance of genome stability is essential to prevent loss of genetic information and the development of diseases such as cancer. One of the most common forms of damage to the genetic code is the oxidation of DNA by reactive oxygen species (ROS), of which 8-oxo-7,8-dihydro-guanine (8-oxoG) is the most frequent modification. Previous studies have established that human single-stranded DNA-binding protein 1 (hSSB1) is essential for the repair of double-stranded DNA breaks by the process of homologous recombination. Here we show that hSSB1 is also required following oxidative damage. Cells lacking hSSB1 are sensitive to oxidizing agents, have deficient ATM and p53 activation and cannot effectively repair 8-oxoGs. Furthermore, we demonstrate that hSSB1 forms a complex with the human oxo-guanine glycosylase 1 (hOGG1) and is important for hOGG1 localization to the damaged chromatin. In vitro, hSSB1 binds directly to DNA containing 8-oxoguanines and enhances hOGG1 activity. These results underpin the crucial role hSSB1 plays as a guardian of the genome.
format Online
Article
Text
id pubmed-4605301
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher Oxford University Press
record_format MEDLINE/PubMed
spelling pubmed-46053012015-10-19 hSSB1 (NABP2/ OBFC2B) is required for the repair of 8-oxo-guanine by the hOGG1-mediated base excision repair pathway Paquet, Nicolas Adams, Mark N. Leong, Vincent Ashton, Nicholas W. Touma, Christine Gamsjaeger, Roland Cubeddu, Liza Beard, Sam Burgess, Joshua T. Bolderson, Emma O'Byrne, Ken J. Richard, Derek J. Nucleic Acids Res Genome Integrity, Repair and Replication The maintenance of genome stability is essential to prevent loss of genetic information and the development of diseases such as cancer. One of the most common forms of damage to the genetic code is the oxidation of DNA by reactive oxygen species (ROS), of which 8-oxo-7,8-dihydro-guanine (8-oxoG) is the most frequent modification. Previous studies have established that human single-stranded DNA-binding protein 1 (hSSB1) is essential for the repair of double-stranded DNA breaks by the process of homologous recombination. Here we show that hSSB1 is also required following oxidative damage. Cells lacking hSSB1 are sensitive to oxidizing agents, have deficient ATM and p53 activation and cannot effectively repair 8-oxoGs. Furthermore, we demonstrate that hSSB1 forms a complex with the human oxo-guanine glycosylase 1 (hOGG1) and is important for hOGG1 localization to the damaged chromatin. In vitro, hSSB1 binds directly to DNA containing 8-oxoguanines and enhances hOGG1 activity. These results underpin the crucial role hSSB1 plays as a guardian of the genome. Oxford University Press 2015-10-15 2015-10-10 /pmc/articles/PMC4605301/ /pubmed/26261212 http://dx.doi.org/10.1093/nar/gkv790 Text en © The Author(s) 2015. 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 Genome Integrity, Repair and Replication
Paquet, Nicolas
Adams, Mark N.
Leong, Vincent
Ashton, Nicholas W.
Touma, Christine
Gamsjaeger, Roland
Cubeddu, Liza
Beard, Sam
Burgess, Joshua T.
Bolderson, Emma
O'Byrne, Ken J.
Richard, Derek J.
hSSB1 (NABP2/ OBFC2B) is required for the repair of 8-oxo-guanine by the hOGG1-mediated base excision repair pathway
title hSSB1 (NABP2/ OBFC2B) is required for the repair of 8-oxo-guanine by the hOGG1-mediated base excision repair pathway
title_full hSSB1 (NABP2/ OBFC2B) is required for the repair of 8-oxo-guanine by the hOGG1-mediated base excision repair pathway
title_fullStr hSSB1 (NABP2/ OBFC2B) is required for the repair of 8-oxo-guanine by the hOGG1-mediated base excision repair pathway
title_full_unstemmed hSSB1 (NABP2/ OBFC2B) is required for the repair of 8-oxo-guanine by the hOGG1-mediated base excision repair pathway
title_short hSSB1 (NABP2/ OBFC2B) is required for the repair of 8-oxo-guanine by the hOGG1-mediated base excision repair pathway
title_sort hssb1 (nabp2/ obfc2b) is required for the repair of 8-oxo-guanine by the hogg1-mediated base excision repair pathway
topic Genome Integrity, Repair and Replication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4605301/
https://www.ncbi.nlm.nih.gov/pubmed/26261212
http://dx.doi.org/10.1093/nar/gkv790
work_keys_str_mv AT paquetnicolas hssb1nabp2obfc2bisrequiredfortherepairof8oxoguaninebythehogg1mediatedbaseexcisionrepairpathway
AT adamsmarkn hssb1nabp2obfc2bisrequiredfortherepairof8oxoguaninebythehogg1mediatedbaseexcisionrepairpathway
AT leongvincent hssb1nabp2obfc2bisrequiredfortherepairof8oxoguaninebythehogg1mediatedbaseexcisionrepairpathway
AT ashtonnicholasw hssb1nabp2obfc2bisrequiredfortherepairof8oxoguaninebythehogg1mediatedbaseexcisionrepairpathway
AT toumachristine hssb1nabp2obfc2bisrequiredfortherepairof8oxoguaninebythehogg1mediatedbaseexcisionrepairpathway
AT gamsjaegerroland hssb1nabp2obfc2bisrequiredfortherepairof8oxoguaninebythehogg1mediatedbaseexcisionrepairpathway
AT cubedduliza hssb1nabp2obfc2bisrequiredfortherepairof8oxoguaninebythehogg1mediatedbaseexcisionrepairpathway
AT beardsam hssb1nabp2obfc2bisrequiredfortherepairof8oxoguaninebythehogg1mediatedbaseexcisionrepairpathway
AT burgessjoshuat hssb1nabp2obfc2bisrequiredfortherepairof8oxoguaninebythehogg1mediatedbaseexcisionrepairpathway
AT boldersonemma hssb1nabp2obfc2bisrequiredfortherepairof8oxoguaninebythehogg1mediatedbaseexcisionrepairpathway
AT obyrnekenj hssb1nabp2obfc2bisrequiredfortherepairof8oxoguaninebythehogg1mediatedbaseexcisionrepairpathway
AT richardderekj hssb1nabp2obfc2bisrequiredfortherepairof8oxoguaninebythehogg1mediatedbaseexcisionrepairpathway