The Emerging Role of the Histone H2AK13/15 Ubiquitination: Mechanisms of Writing, Reading, and Erasing in DNA Damage Repair and Disease
Abstract
:1. Introduction
2. Writing: RNF168-Mediated H2AK13/15ub
2.1. Discovery, Function, and Domain Composition of RNF168
2.2. RNF168 Specifically Ubiquitinates Nucleosomal H2AK13/15 Sites
2.3. Crosstalk of H1 Ubiquitination and H2AK13/15 Ubiquitination
3. Reading: Effector Proteins of H2AK13/15ub
3.1. 53BP1
3.1.1. Mono-Ubiquitinated H2AK15 Recognition by 53BP1
3.1.2. Di-Ubiquitinated H2AK13/15 Recognition by 53BP1
3.1.3. The Second-Tier Modifications of H2AK15ub: K6ac, T12ph
3.1.4. 53BP1 Recruitment Influenced by Other Histone Modifications
3.2. RAD18
3.3. BARD1
3.3.1. Discovery and Functionality of BARD1
3.3.2. Mechanism of BARD1 Recognition of H2AK13/15ub
4. Erasing: H2AK13/15 Deubiquitinases
4.1. USP3
4.2. USP16
4.3. USP44
4.4. USP51
4.5. POH1
5. H2AK13/15 Ubiquitination and Disease
5.1. RIDDLE Syndrome
5.2. Neurological Diseases
5.3. Immune System Diseases
5.4. Breast Cancer
6. Conclusions and Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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53BP1 Domain | Histone Modification | Influence | Refs. |
---|---|---|---|
Tudor | H4K20me2 H4K16me1 | Enhance binding | [21,68] |
UDR | H2AK15monoub H2AK15diub H2AK13diub | Enhance binding | [21,66,67] |
H2AK15UbT12ph H2AK15UbK6ac | Impair binding | [70,71] | |
BRCT | γH2AXS139 | Enhance binding | [69,72] |
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Shu, Q.; Liu, Y.; Ai, H. The Emerging Role of the Histone H2AK13/15 Ubiquitination: Mechanisms of Writing, Reading, and Erasing in DNA Damage Repair and Disease. Cells 2025, 14, 307. https://doi.org/10.3390/cells14040307
Shu Q, Liu Y, Ai H. The Emerging Role of the Histone H2AK13/15 Ubiquitination: Mechanisms of Writing, Reading, and Erasing in DNA Damage Repair and Disease. Cells. 2025; 14(4):307. https://doi.org/10.3390/cells14040307
Chicago/Turabian StyleShu, Qi, Yun Liu, and Huasong Ai. 2025. "The Emerging Role of the Histone H2AK13/15 Ubiquitination: Mechanisms of Writing, Reading, and Erasing in DNA Damage Repair and Disease" Cells 14, no. 4: 307. https://doi.org/10.3390/cells14040307
APA StyleShu, Q., Liu, Y., & Ai, H. (2025). The Emerging Role of the Histone H2AK13/15 Ubiquitination: Mechanisms of Writing, Reading, and Erasing in DNA Damage Repair and Disease. Cells, 14(4), 307. https://doi.org/10.3390/cells14040307