Ubiquitin and Ubiquitin-Like Proteins Are Essential Regulators of DNA Damage Bypass
Abstract
:Simple Summary
Abstract
1. Introduction
2. Ubiquitin and Ubiquitin-Like Modifiers
3. DNA Damage Bypass
4. Ubiquitin and Ubiquitin-Like Modifiers in DNA Damage Bypass
4.1. PCNA Ubiquitination Is a Central Regulator of Translesion Synthesis and Template Switching
4.2. PCNA Can Also Be Modified by SUMOylation
4.3. PCNA Monoubiquitination Is Negatively Regulated by NEDDylation and ISGylation
4.4. PCNA Monoubiquitination Is Opposed by Deubiquitinating Enzymes
4.5. TLS Polymerases Are also Regulated by Ubiquitin and Ubiquitin-Like Proteins
5. DNA Damage Bypass and Cancer
5.1. Deregulation of DNA Damage Bypass in Cancer
5.2. Targeting DNA Damage Bypass in Cancer Therapies
6. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Protein | Role in DNA Damage Response | Associated Cancers |
---|---|---|
Pol η | Y family TLS polymerase | Mutations/defects implicated in XP-V syndrome (high cancer susceptibility) [96] Upregulated in: bladder, non-small cell lung cancer, head and neck squamous cell carcinoma, ovarian cancer stem cells [97,98,99] |
Pol ι | Y family TLS polymerase | Upregulated in: bladder cancer, breast cancer, basal cell carcinoma, esophageal squamous cell carcinoma, glioma (correlated with lymph node metastasis) [100,101,102,103,104] SNPs associated with prostate cancer, adenocarcinoma, squamous cell carcinoma [85,86] |
Pol κ | Y family TLS polymerase | Mutations/defects implicated in prostate cancer, breast cancer [105,106] Upregulated in: glioma, non-small cell lung cancer [104,107] |
Rev1 | Y family TLS polymerase | Upregulated in: prostate cancer [108] SNPs associated with cervical squamous cell carcinoma [109] |
PCNA | DNA sliding clamp | Upregulated in: prostate cancer, ovarian cancer (especially with lymph node metastasis) [110,111] |
Rad18 | E3 ubiquitin ligase | Upregulated in: colorectal cancer, primary and metastatic melanoma, glioma [90,112,113] |
HLTF | E3 ubiquitin ligase | Downregulated in: colorectal, colon, stomach cancer, esophageal squamous cell carcinoma [114,115,116,117] |
ATAD5 | Unloading of PCNA from DNA strand | Mutations/defects associated with endometrial carcinoma [118] Upregulated in: epithelial ovarian carcinoma [119] |
SPRTN | Stabilizing PCNA, resolving fork stalling DNA-protein crosslinks | Mutations/defects implicated in hepatocellular carcinoma [120] |
USP1 | Deubiquitinating enzyme | Upregulated in: cervical, stomach cancer, melanoma, sarcoma, osteosarcoma [121,122] |
USP7 | Deubiquitinating enzyme | Upregulated in: hepatocellular carcinoma, non-small cell lung cancer, epithelial ovarian cancer, myeloma [123,124,125,126] |
USP10 | Deubiquitinating enzyme | Upregulated in: prostate cancer, hepatocellular carcinoma [127,128] |
NEDP1 | De-NEDDylating enzyme | Downregulated in: hepatocellular carcinoma [129] |
ISG15 | Ubiquitin-like protein | Upregulated in: bladder, breast, endometrium, prostate cancer, hepatocellular carcinoma [130,131,132,133] |
NEDD8 | Ubiquitin-like protein | Upregulated in: hepatocellular carcinoma, nasopharyngeal carcinoma (correlated with lymph node metastasis) [134,135] |
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Wilkinson, N.A.; Mnuskin, K.S.; Ashton, N.W.; Woodgate, R. Ubiquitin and Ubiquitin-Like Proteins Are Essential Regulators of DNA Damage Bypass. Cancers 2020, 12, 2848. https://doi.org/10.3390/cancers12102848
Wilkinson NA, Mnuskin KS, Ashton NW, Woodgate R. Ubiquitin and Ubiquitin-Like Proteins Are Essential Regulators of DNA Damage Bypass. Cancers. 2020; 12(10):2848. https://doi.org/10.3390/cancers12102848
Chicago/Turabian StyleWilkinson, Nicole A., Katherine S. Mnuskin, Nicholas W. Ashton, and Roger Woodgate. 2020. "Ubiquitin and Ubiquitin-Like Proteins Are Essential Regulators of DNA Damage Bypass" Cancers 12, no. 10: 2848. https://doi.org/10.3390/cancers12102848