ArticleScientific reports2017
Cdc7-Dbf4-mediated phosphorylation of HSP90-S164 stabilizes HSP90-HCLK2-MRN complex to enhance ATR/ATM signaling that overcomes replication stress in cancer.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 29 citations in OpenAlex.
- Exploring the multifaceted Dbf4-dependent kinase from temporal, spatial, and substrate repertoire perspectives.Communications biology · 2026Review
- The role of coronary computed tomography angiography in coronary bifurcation disease: a scoping review.The international journal of cardiovascular imaging · 2026Article
- Pan-cancer analysis identifies DBF4B as an immunologic and prognostic biomarker.Journal of Cancer · 2025Article
- Protein kinase Cdc7 supports viral replication by phosphorylatingJournal of virology · 2023Article
- Minichromosome maintenance proteins in lung adenocarcinoma: Clinical significance and therapeutic targets.FEBS open bio · 2023Article
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- The Role of Hsp90-R2TP in Macromolecular Complex Assembly and Stabilization.Biomolecules · 2022Review
- Combined Dusp4 and p53 loss with Dbf4 amplification drives tumorigenesis via cell cycle restriction and replication stress escape in breast cancer.Breast cancer research : BCR · 2022Article
- Emerging Link between Tsc1 and FNIP Co-Chaperones of Hsp90 and Cancer.Biomolecules · 2022Review
- Identification and Validation of a Prognostic Model Based on Three MVI-Related Genes in Hepatocellular Carcinoma.International journal of biological sciences · 2022Article
- Lamin-A interacting protein Hsp90 is required for DNA damage repair and chemoresistance of ovarian cancer cells.Cell death & disease · 2021Article
- Post-translational modifications of Hsp90 and translating the chaperone code.The Journal of biological chemistry · 2020Review
- CDC7 kinase promotes MRE11 fork processing, modulating fork speed and chromosomal breakage.EMBO reports · 2020Article
- Heat-shock proteins: chaperoning DNA repair.Oncogene · 2020Review
- Identification of Novel Cdc7 Kinase Inhibitors as Anti-Cancer Agents that Target the Interaction with Dbf4 by the Fragment Complementation and Drug Repositioning Approach.EBioMedicine · 2018Article
- Role of MCM2-7 protein phosphorylation in human cancer cells.Cell & bioscience · 2018Review
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Authors and funding
13 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cdc7-Dbf4 kinase plays a key role in the initiation of DNA replication and contributes to the replication stress in cancer. The activity of human Cdc7-Dbf4 kinase remains active and acts as an effector of checkpoint under replication stress. However, the downstream targets of Cdc7-Dbf4 contributed to checkpoint regulation and replication stress-support function in cancer are not fully identified. In this work, we showed that aberrant Cdc7-Dbf4 induces DNA lesions that activate ATM/ATR-mediated checkpoint and homologous recombination (HR) DNA repair. Using a phosphoproteome approach, we identified HSP90-S164 as a target of Cdc7-Dbf4 in vitro and in vivo. The phosphorylation of HSP90-S164 by Cdc7-Dbf4 is required for the stability of HSP90-HCLK2-MRN complex and the function of ATM/ATR signaling cascade and HR DNA repair. In clinically, the phosphorylation of HSP90-S164 indeed is increased in oral cancer patients. Our results indicate that aberrant Cdc7-Dbf4 enhances replication stress tolerance by rewiring ATR/ATM mediated HR repair through HSP90-S164 phosphorylation and by promoting recovery from replication stress. We provide a new solution to a subtyping of cancer patients with dominant ATR/HSP90 expression by combining inhibitors of ATR-Chk1, HSP90, or Cdc7 in cancer combination therapy.
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