Chromatin remodelling complex RSC promotes base excision repair in chromatin of Saccharomyces cerevisiae

Wioletta Czaja; Peng Mao; Michael J. Smerdon

doi:10.1016/j.dnarep.2014.01.002

Chromatin remodelling complex RSC promotes base excision repair in chromatin of Saccharomyces cerevisiae

Wioletta Czaja, Peng Mao, Michael J. Smerdon

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26 Scopus citations

Abstract

The base excision repair (BER) pathway is a conserved DNA repair system required to maintain genomic integrity and prevent mutagenesis in all eukaryotic cells. Nevertheless, how BER operates in vivo (i.e. in the context of chromatin) is poorly understood. We have investigated the role of an essential ATP-dependent chromatin remodelling (ACR) complex RSC (Remodels the Structure of Chromatin) in BER of intact yeast cells. We show that depletion of STH1, the ATPase subunit of RSC, causes enhanced sensitivity to the DNA alkylating agent methyl methanesulfonate (MMS) and results in a substantial inhibition of BER, at the GAL1 locus and in the genome overall. Consistent with this observation, the DNA in chromatin is less accessible to micrococcal nuclease digestion in the absence of RSC. Quantitative PCR results indicate that repair deficiency in STH1 depleted cells is not due to changes in the expression of BER genes. Collectively, our data indicates the RSC complex promotes efficient BER in chromatin. These results provide, for the first time, a link between ATP-dependent chromatin remodelling and BER in living cells.

Original language	English (US)
Pages (from-to)	35-43
Number of pages	9
Journal	DNA Repair
Volume	16
Issue number	1
DOIs	https://doi.org/10.1016/j.dnarep.2014.01.002
State	Published - Apr 2014
Externally published	Yes

Bibliographical note

Funding Information:
This work was made possible by National Institutes of Health grant ES002614 from the National Institute of Environmental Health Sciences (NIEHS) . The contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIEHS, NIH.

Keywords

Alkylated DNA damage
MMS
Nucleosome
SWI/SNF

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title = "Chromatin remodelling complex RSC promotes base excision repair in chromatin of Saccharomyces cerevisiae",

abstract = "The base excision repair (BER) pathway is a conserved DNA repair system required to maintain genomic integrity and prevent mutagenesis in all eukaryotic cells. Nevertheless, how BER operates in vivo (i.e. in the context of chromatin) is poorly understood. We have investigated the role of an essential ATP-dependent chromatin remodelling (ACR) complex RSC (Remodels the Structure of Chromatin) in BER of intact yeast cells. We show that depletion of STH1, the ATPase subunit of RSC, causes enhanced sensitivity to the DNA alkylating agent methyl methanesulfonate (MMS) and results in a substantial inhibition of BER, at the GAL1 locus and in the genome overall. Consistent with this observation, the DNA in chromatin is less accessible to micrococcal nuclease digestion in the absence of RSC. Quantitative PCR results indicate that repair deficiency in STH1 depleted cells is not due to changes in the expression of BER genes. Collectively, our data indicates the RSC complex promotes efficient BER in chromatin. These results provide, for the first time, a link between ATP-dependent chromatin remodelling and BER in living cells.",

keywords = "Alkylated DNA damage, MMS, Nucleosome, SWI/SNF",

author = "Wioletta Czaja and Peng Mao and Smerdon, {Michael J.}",

note = "Funding Information: This work was made possible by National Institutes of Health grant ES002614 from the National Institute of Environmental Health Sciences (NIEHS) . The contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIEHS, NIH. ",

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AU - Czaja, Wioletta

AU - Mao, Peng

AU - Smerdon, Michael J.

N1 - Funding Information: This work was made possible by National Institutes of Health grant ES002614 from the National Institute of Environmental Health Sciences (NIEHS) . The contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIEHS, NIH.

PY - 2014/4

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N2 - The base excision repair (BER) pathway is a conserved DNA repair system required to maintain genomic integrity and prevent mutagenesis in all eukaryotic cells. Nevertheless, how BER operates in vivo (i.e. in the context of chromatin) is poorly understood. We have investigated the role of an essential ATP-dependent chromatin remodelling (ACR) complex RSC (Remodels the Structure of Chromatin) in BER of intact yeast cells. We show that depletion of STH1, the ATPase subunit of RSC, causes enhanced sensitivity to the DNA alkylating agent methyl methanesulfonate (MMS) and results in a substantial inhibition of BER, at the GAL1 locus and in the genome overall. Consistent with this observation, the DNA in chromatin is less accessible to micrococcal nuclease digestion in the absence of RSC. Quantitative PCR results indicate that repair deficiency in STH1 depleted cells is not due to changes in the expression of BER genes. Collectively, our data indicates the RSC complex promotes efficient BER in chromatin. These results provide, for the first time, a link between ATP-dependent chromatin remodelling and BER in living cells.

AB - The base excision repair (BER) pathway is a conserved DNA repair system required to maintain genomic integrity and prevent mutagenesis in all eukaryotic cells. Nevertheless, how BER operates in vivo (i.e. in the context of chromatin) is poorly understood. We have investigated the role of an essential ATP-dependent chromatin remodelling (ACR) complex RSC (Remodels the Structure of Chromatin) in BER of intact yeast cells. We show that depletion of STH1, the ATPase subunit of RSC, causes enhanced sensitivity to the DNA alkylating agent methyl methanesulfonate (MMS) and results in a substantial inhibition of BER, at the GAL1 locus and in the genome overall. Consistent with this observation, the DNA in chromatin is less accessible to micrococcal nuclease digestion in the absence of RSC. Quantitative PCR results indicate that repair deficiency in STH1 depleted cells is not due to changes in the expression of BER genes. Collectively, our data indicates the RSC complex promotes efficient BER in chromatin. These results provide, for the first time, a link between ATP-dependent chromatin remodelling and BER in living cells.

KW - Alkylated DNA damage

KW - MMS

KW - Nucleosome

KW - SWI/SNF

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Chromatin remodelling complex RSC promotes base excision repair in chromatin of Saccharomyces cerevisiae

Abstract

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