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

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

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Item Type: Article
Status: Published
Official URL: https://doi.org/10.1007/s00018-020-03552-5
Journal or Publication Title: Cellular and Molecular Life Sciences
Date: 2020
Divisions: Gene and Stem Cell Therapy
Depositing User: General Admin
Identification Number: 10.1007/s00018-020-03552-5
ISSN: 1420-682X
Date Deposited: 03 Jan 2021 23:59

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.

Cole, Alexander J.
Dickson, Kristie-Ann
Liddle, Christopher
Stirzaker, Clare
Shah, Jaynish S.
Clifton-Bligh, Roderick
Marsh, Deborah J.
Last Modified: 03 Jan 2021 23:59
URI: https://eprints.centenary.org.au/id/eprint/826

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