ArticleOncotarget2017
BMI1 reduces ATR activation and signalling caused by hydroxyurea.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
5 citing papers in PubMed, 1 synthesis or guideline pooled it, 9 citations in OpenAlex.
- Assessment of biochemical recurrence of prostate cancer (Review).International journal of oncology · 2019Pooled it
- Factors Influencing the Central Nervous System (CNS) Distribution of the Ataxia Telangiectasia Mutated and Rad3-Related Inhibitor Elimusertib (BAY1895344): Implications for the Treatment of CNS Tumors.The Journal of pharmacology and experimental therapeutics · 2024Article
- Targeting BMI-1 to deplete antibody-secreting cells in autoimmunity.Clinical & translational immunology · 2023Article
- Transcription-replication conflicts as a source of common fragile site instability caused by BMI1-RNF2 deficiency.PLoS genetics · 2020Article
- The Contributions of Prostate Cancer Stem Cells in Prostate Cancer Initiation and Metastasis.Cancers · 2019Review
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BMI1 facilitates DNA damage response (DDR) induced by double strand DNA breaks; however, it remains unknown whether BMI1 functions in single strand DNA (ssDNA) lesions-initiated DDR. We report here that BMI1 reduces hydroxyurea-elicited ATR activation, thereby reducing the S-phase checkpoints. Hydroxyurea induces ssDNA lesions, which activate ATR through binding TOPBP1 as evidenced by phosphorylation of ATR at threonine 1989 (ATRpT1989). ATR subsequently phosphorylates H2AX at serine 139 (γH2AX) and CHK1 at serine 345 (CHK1pS345), leading to phosphorylation of CDK1 at tyrosine 15 (CDK1pY15) and S-phase arrest. BMI1 overexpression reduced γH2AX, CHK1pS345, CDK1pY15, S-phase arrest, and ATR activation in HU-treated MCF7 and DU145 cells, whereas BMI1 knockdown enhanced these events. BMI1 contains a ring finger, helix-turn, proline/serine domain and two nuclear localization signals (NLS). Individual deletion of these domains did not abolish BMI1-derived reductions of CHK1pS345 in MCF7 cells following HU exposure, suggesting that these structural features are not essential for BMI1 to attenuate ATR-mediated CHK1pS345. BMI1 interacts with both TOPBP1 and ATR. Furthermore, all of our BMI1 mutants associate with endogenous TOPBP1. It has previously been established that association of TOPBP1 and ATR is required for ATR activation. Thus, our results suggest that BMI1 decreases ATR activation through a mechanism that involves binding to TOPBP1 and/or ATR.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.