ArticleScientific reports2019
HERC2 regulates RPA2 by mediating ATR-induced Ser33 phosphorylation and ubiquitin-dependent degradation.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 21 citations in OpenAlex.
- microRNA miR-31-5p confers protection to melanin-deficient vitiligo keratinocytes against UV-B induced DNA damage by activating autophagy machinery.Scientific reports · 2026Article
- Loss of MNX1 Sensitizes Tumors to Cytotoxic T Cells by Degradation of PD-L1 mRNA.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Combined inhibition of RAD51 and CHK1 causes synergistic toxicity in cisplatin resistant cancer cells by triggering replication fork collapse.International journal of cancer · 2025Article
- Therapy-induced secretion of spliceosomal components mediates pro-survival crosstalk between ovarian cancer cells.Nature communications · 2024Article
- Proteomics Analysis of the Polyomavirus DNA Replication Initiation Complex Reveals Novel Functional Phosphorylated Residues and Associated Proteins.International journal of molecular sciences · 2024Article
- Review
- Upregulated RPA2 in endometrial tissues of repeated implantation failure patients impairs the endometrial decidualization.Journal of assisted reproduction and genetics · 2023Article
- Pharmacological Ascorbate Elicits Anti-Cancer Activities against Non-Small Cell Lung Cancer through Hydrogen-Peroxide-Induced-DNA-Damage.Antioxidants (Basel, Switzerland) · 2023Article
- Long non-coding RNA PCAT19 safeguards DNA in quiescent endothelial cells by preventing uncontrolled phosphorylation of RPA2.Cell reports · 2022Article
- Review
- Review
- HERC2 inactivation abrogates nucleolar localization of RecQ helicases BLM and WRN.Scientific reports · 2021Article
- Valproic Acid Regulates HR and Cell Cycle Through MUS81-pRPA2 Pathway in Response to Hydroxyurea.Frontiers in oncology · 2021Article
- HERC Ubiquitin Ligases in Cancer.Cancers · 2020Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Replication protein A (RPA) binds to and stabilizes single-stranded DNA and is essential for the genome stability. We reported that an E3 ubiquitin ligase, HERC2, suppresses G-quadruplex (G4) DNA by regulating RPA-helicase complexes. However, the precise mechanism of HERC2 on RPA is as yet largely unknown. Here, we show essential roles for HERC2 on RPA2 status: induction of phosphorylation and degradation of the modified form. HERC2 interacted with RPA through the C-terminal HECT domain. Ubiquitination of RPA2 was inhibited by HERC2 depletion and rescued by reintroduction of the C-terminal fragment of HERC2. ATR-mediated phosphorylation of RPA2 at Ser33 induced by low-level replication stress was inhibited by depletion of HERC2. Contrary, cells lacking HERC2 catalytic residues constitutively expressed an increased level of Ser33-phosphorylated RPA2. HERC2-mediated ubiquitination of RPA2 was abolished by an ATR inhibitor, supporting a hypothesis that the ubiquitinated RPA2 is a phosphorylated subset. Functionally, HERC2 E3 activity has an epistatic relationship with RPA in the suppression of G4 when judged with siRNA knockdown experiments. Together, these results suggest that HERC2 fine-tunes ATR-phosphorylated RPA2 levels through induction and degradation, a mechanism that could be critical for the suppression of secondary DNA structures during cell proliferation.
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