Ubiquitin chromatin remodelling after DNA damage is associated with the expression of key cancer genes and pathways.

Cole, AJ; Dickson, K-A; Liddle, C; Stirzaker, C; Shah, JS; Clifton-Bligh, R; Marsh, DJ

Ubiquitin chromatin remodelling after DNA damage is associated with the expression of key cancer genes and pathways.

Cole, AJ Dickson, K-A Liddle, C Stirzaker, C Shah, JS Clifton-Bligh, R Marsh, DJ

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Publisher:: SPRINGER BASEL AG
Publication Type:: Journal Article
Citation:: Cellular and molecular life sciences : CMLS, 2020
Issue Date:: 2020-05-26

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Field	Value	Language
dc.contributor.author	Cole, AJ
dc.contributor.author	Dickson, K-A
dc.contributor.author	Liddle, C
dc.contributor.author	Stirzaker, C
dc.contributor.author	Shah, JS
dc.contributor.author	Clifton-Bligh, R
dc.contributor.author	Marsh, DJ
dc.date.accessioned	2020-11-23T03:41:12Z
dc.date.available	2020-05-13
dc.date.available	2020-11-23T03:41:12Z
dc.date.issued	2020-05-26
dc.identifier.citation	Cellular and molecular life sciences : CMLS, 2020
dc.identifier.issn	1420-9071
dc.identifier.issn	1420-9071
dc.identifier.uri	http://hdl.handle.net/10453/144249
dc.description.abstract	Modification of the cancer-associated chromatin landscape in response to therapeutic DNA damage influences gene expression and contributes to cell fate. The central histone mark H2Bub1 results from addition of a single ubiquitin on lysine 120 of histone H2B and is an important regulator of gene expression. Following treatment with a platinum-based chemotherapeutic, there is a reduction in global levels of H2Bub1 accompanied by an increase in levels of the tumor suppressor p53. Although total H2Bub1 decreases following DNA damage, H2Bub1 is enriched downstream of transcription start sites of specific genes. Gene-specific H2Bub1 enrichment was observed at a defined group of genes that clustered into cancer-related pathways and correlated with increased gene expression. H2Bub1-enriched genes encompassed fifteen p53 target genes including PPM1D, BTG2, PLK2, MDM2, CDKN1A and BBC3, genes related to ERK/MAPK signalling, those participating in nucleotide excision repair including XPC, and genes involved in the immune response and platinum drug resistance including POLH. Enrichment of H2Bub1 at key cancer-related genes may function to regulate gene expression and influence the cellular response to therapeutic DNA damage.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	SPRINGER BASEL AG
dc.relation	http://purl.org/au-research/grants/nhmrc/1004799
dc.relation	http://purl.org/au-research/grants/arc/FT100100489
dc.relation.ispartof	Cellular and molecular life sciences : CMLS
dc.relation.isbasedon	10.1007/s00018-020-03552-5
dc.rights	info:eu-repo/semantics/restrictedAccess
dc.subject	0601 Biochemistry and Cell Biology, 0606 Physiology, 1103 Clinical Sciences
dc.subject.classification	Biochemistry & Molecular Biology
dc.title	Ubiquitin chromatin remodelling after DNA damage is associated with the expression of key cancer genes and pathways.
dc.type	Journal Article
utslib.location.activity	Switzerland
utslib.for	0601 Biochemistry and Cell Biology
utslib.for	0606 Physiology
utslib.for	1103 Clinical Sciences
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney
utslib.copyright.status	closed_access	*
dc.date.updated	2020-11-23T03:41:08Z
pubs.publication-status	Published

Abstract:

Modification of the cancer-associated chromatin landscape in response to therapeutic DNA damage influences gene expression and contributes to cell fate. The central histone mark H2Bub1 results from addition of a single ubiquitin on lysine 120 of histone H2B and is an important regulator of gene expression. Following treatment with a platinum-based chemotherapeutic, there is a reduction in global levels of H2Bub1 accompanied by an increase in levels of the tumor suppressor p53. Although total H2Bub1 decreases following DNA damage, H2Bub1 is enriched downstream of transcription start sites of specific genes. Gene-specific H2Bub1 enrichment was observed at a defined group of genes that clustered into cancer-related pathways and correlated with increased gene expression. H2Bub1-enriched genes encompassed fifteen p53 target genes including PPM1D, BTG2, PLK2, MDM2, CDKN1A and BBC3, genes related to ERK/MAPK signalling, those participating in nucleotide excision repair including XPC, and genes involved in the immune response and platinum drug resistance including POLH. Enrichment of H2Bub1 at key cancer-related genes may function to regulate gene expression and influence the cellular response to therapeutic DNA damage.

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http://hdl.handle.net/10453/144249