ArticlePLoS biology2016
Wuho Is a New Member in Maintaining Genome Stability through its Interaction with Flap Endonuclease 1.
Article in PLoS biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 27 citations in OpenAlex.
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- tRNA Modifications and Dysregulation: Implications for Brain Diseases.Brain sciences · 2024Review
- Advances in brain epitranscriptomics research and translational opportunities.Molecular psychiatry · 2024Review
- WDR4 promotes the progression and lymphatic metastasis of bladder cancer via transcriptional down-regulation of ARRB2.Oncogenesis · 2023Article
- Wdr4 promotes cerebellar development and locomotion through Arhgap17-mediated Rac1 activation.Cell death & disease · 2023Article
- Small-Molecule Inhibitors Targeting FEN1 for Cancer Therapy.Biomolecules · 2022Review
- Genetic Association of the FunctionalJournal of personalized medicine · 2021Article
- Article
- WD40 protein Wuho controls germline homeostasis via TRIM-NHL tumor suppressor Mei-p26 inDevelopment (Cambridge, England) · 2020Article
- KHDC3L mutation causes recurrent pregnancy loss by inducing genomic instability of human early embryonic cells.PLoS biology · 2019Article
- Structural basis of 5' flap recognition and protein-protein interactions of human flap endonuclease 1.Nucleic acids research · 2018Article
- Ubiquitination of tumor suppressor PML regulates prometastatic and immunosuppressive tumor microenvironment.The Journal of clinical investigation · 2017Article
- Control of structure-specific endonucleases to maintain genome stability.Nature reviews. Molecular cell biology · 2017Review
- Interacting partners of FEN1 and its role in the development of anticancer therapeutics.Oncotarget · 2017Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Replication forks are vulnerable to wayward nuclease activities. We report here our discovery of a new member in guarding genome stability at replication forks. We previously isolated a Drosophila mutation, wuho (wh, no progeny), characterized by a severe fertility defect and affecting expression of a protein (WH) in a family of conserved proteins with multiple WD40 repeats. Knockdown of WH by siRNA in Drosophila, mouse, and human cultured cells results in DNA damage with strand breaks and apoptosis through ATM/Chk2/p53 signaling pathway. Mice with mWh knockout are early embryonic lethal and display DNA damage. We identify that the flap endonuclease 1 (FEN1) is one of the interacting proteins. Fluorescence microscopy showed the localization of WH at the site of nascent DNA synthesis along with other replication proteins, including FEN1 and PCNA. We show that WH is able to modulate FEN1's endonucleolytic activities depending on the substrate DNA structure. The stimulatory or inhibitory effects of WH on FEN1's flap versus gap endonuclease activities are consistent with the proposed WH's functions in protecting the integrity of replication fork. These results suggest that wh is a new member of the guardians of genome stability because it regulates FEN1's potential DNA cleavage threat near the site of replication.
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