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

Nicolas Paquet; Mark N. Adams; Vincent Leong; Nicholas W. Ashton; Christine Touma; Roland Gamsjaeger; Liza Cubeddu; Sam Beard; Joshua T. Burgess; Emma Bolderson; Ken J. O’Byrne; Derek J. Richard

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

Nicolas Paquet, Mark N. Adams, Vincent Leong, Nicholas W. Ashton, Christine Touma, Roland Gamsjaeger, Liza Cubeddu, Sam Beard, Joshua T. Burgess, Emma Bolderson, Ken J. O’Byrne, Derek J. Richard

Research output: Contribution to journal › Article › peer-review

38 Citations (Scopus)

Abstract

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 oxoguanine 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.

Original language	English
Pages (from-to)	8817-8829
Number of pages	13
Journal	Nucleic Acids Research
Volume	43
Issue number	18
Publication status	Published - 10 Aug 2015

Bibliographical note

Publisher Copyright:
© 2015 The Author(s). Published by Oxford University Press on behalf of Nucleic Acids Research.

Keywords

DNA-binding proteins
cancer
human genome

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Cite this

@article{dabe384f3fd94c0e9aebcf8571cd416e,

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

abstract = "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 oxoguanine 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.",

keywords = "DNA-binding proteins, cancer, human genome",

author = "Nicolas Paquet and Adams, {Mark N.} and Vincent Leong and Ashton, {Nicholas W.} and Christine Touma and Roland Gamsjaeger and Liza Cubeddu and Sam Beard and Burgess, {Joshua T.} and Emma Bolderson and O{\textquoteright}Byrne, {Ken J.} and Richard, {Derek J.}",

note = "Publisher Copyright: {\textcopyright} 2015 The Author(s). Published by Oxford University Press on behalf of Nucleic Acids Research.",

year = "2015",

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language = "English",

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pages = "8817--8829",

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TY - JOUR

T1 - hSSB1 (NABP2/ OBFC2B) is required for the repair of 8-oxo-guanine by the hOGG1-mediated base excision repair pathway

AU - Paquet, Nicolas

AU - Adams, Mark N.

AU - Leong, Vincent

AU - Ashton, Nicholas W.

AU - Touma, Christine

AU - Gamsjaeger, Roland

AU - Cubeddu, Liza

AU - Beard, Sam

AU - Burgess, Joshua T.

AU - Bolderson, Emma

AU - O’Byrne, Ken J.

AU - Richard, Derek J.

PY - 2015/8/10

Y1 - 2015/8/10

N2 - 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 oxoguanine 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.

AB - 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 oxoguanine 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.

KW - DNA-binding proteins

KW - cancer

KW - human genome

UR - http://handle.uws.edu.au:8081/1959.7/uws:32479

M3 - Article

SN - 0305-1048

VL - 43

SP - 8817

EP - 8829

JO - Nucleic Acids Research

JF - Nucleic Acids Research

IS - 18

ER -

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

Abstract

Bibliographical note

Keywords

UN SDGs

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