Journal article
Multiple interaction nodes define the post‐replication repair response to UV‐induced DNA damage that is defective in melanomas and correlated with UV signature mutation load
Molecular Oncology, Vol.14(1), pp.22-41
2020
Abstract
Ultraviolet radiation-induced DNA mutations are a primary environmental driver of melanoma. The reason for this very high level of unrepaired DNA lesions leading to these mutations is still poorly understood. The primary DNA repair mechanism for UV-induced lesions, the nucleotide excision repair pathway, appears intact in most melanomas. We have previously reported a post-replication repair mechanism that is commonly defective in melanoma cell lines. Here we have used a genome wide approach to identify the components of this post-replication repair mechanism. We have used differential transcript polysome loading to identify transcripts that are associated with the UV response, then functionally assessed these to identify novel components of this repair and cell cycle checkpoint network. We have identified multiple interaction nodes, including global genomic nucleotide excision repair and homologous recombination repair, and previously unexpected MASTL pathway as components of the response. Finally, we have used bioinformatics to assess the contribution of dysregulated expression of these pathways to the UV signature mutation load of a large melanoma cohort. We show that dysregulation of the pathway, especially the DNA damage repair components, are significant contributors to UV mutation load, and that dysregulation of the MASTL pathway appears to be a significant contributor to high UV signature mutation load.
Details
- Title
- Multiple interaction nodes define the post‐replication repair response to UV‐induced DNA damage that is defective in melanomas and correlated with UV signature mutation load
- Authors
- Sandra Pavey (Author) - The University of QueenslandAlex Pinder (Author) - The University of QueenslandWinnie Fernando (Author) - The University of QueenslandNicholas D'Arcy (Author) - The University of QueenslandNicholas Matigian (Author) - The University of QueenslandDubravka Skalamera (Author) - The University of QueenslandKim-Anh Le Cao (Author) - The University of QueenslandDorothy Loo-Oey (Author) - The University of QueenslandMichelle M Hill (Author) - The University of QueenslandMitchell Stark (Author) - The University of QueenslandMichael G Kimlin (Author) - University of the Sunshine Coast, QueenslandAndrew Burgess (Author) - Anzac Research InstituteNicole Cloonan (Author) - QIMR Berghofer Medical Research InstituteRichard A Sturm (Author) - The University of QueenslandBrian Gabrielli (Corresponding Author) - The University of Queensland
- Publication details
- Molecular Oncology, Vol.14(1), pp.22-41
- Publisher
- John Wiley & Sons Ltd.
- Date published
- 2020
- DOI
- 10.1002/1878-0261.12601
- ISSN
- 1574-7891
- Copyright note
- Copyright © 2019 The Authors. Published by FEBS Press and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- Organisation Unit
- University of the Sunshine Coast, Queensland; School of Health and Sport Sciences - Legacy
- Language
- English
- Record Identifier
- 99450736902621
- Output Type
- Journal article
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