Affordable Access

deepdyve-link
Publisher Website

Ubiquitin-like proteins in the DNA damage response: the next generation.

Authors
  • Da Costa, Isabelle C1
  • Schmidt, Christine K1
  • 1 Manchester Cancer Research Centre, Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, 555 Wilmslow Road, Manchester, M20 4GJ, U.K.
Type
Published Article
Journal
Essays in biochemistry
Publication Date
Oct 26, 2020
Volume
64
Issue
5
Pages
737–752
Identifiers
DOI: 10.1042/EBC20190095
PMID: 32451552
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

DNA suffers constant insult from a variety of endogenous and exogenous sources. To deal with the arising lesions, cells have evolved complex and coordinated pathways, collectively termed the DNA damage response (DDR). Importantly, an improper DDR can lead to genome instability, premature ageing and human diseases, including cancer as well as neurodegenerative disorders. As a crucial process for cell survival, regulation of the DDR is multi-layered and includes several post-translational modifications. Since the discovery of ubiquitin in 1975 and the ubiquitylation cascade in the early 1980s, a number of ubiquitin-like proteins (UBLs) have been identified as post-translational modifiers. However, while the importance of ubiquitin and the UBLs SUMO and NEDD8 in DNA damage repair and signalling is well established, the roles of the remaining UBLs in the DDR are only starting to be uncovered. Herein, we revise the current status of the UBLs ISG15, UBL5, FAT10 and UFM1 as emerging co-regulators of DDR processes. In fact, it is becoming clear that these post-translational modifiers play important pleiotropic roles in DNA damage and/or associated stress-related cellular responses. Expanding our understanding of the molecular mechanisms underlying these emerging UBL functions will be fundamental for enhancing our knowledge of the DDR and potentially provide new therapeutic strategies for various human diseases including cancer. © 2020 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Report this publication

Statistics

Seen <100 times