ArticlePloS one2013
Tousled-like kinase-dependent phosphorylation of Rad9 plays a role in cell cycle progression and G2/M checkpoint exit.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 38 citations in OpenAlex.
- Co-Phosphoregulatory Network Underlying Functional Coherence of TLK1 and TLK2 Kinase Paralogs.International journal of molecular sciences · 2026Article
- Autophosphorylation of the Tousled-like kinases TLK1 and TLK2 regulates recruitment to damaged chromatin via PCNA interaction.Nucleic acids research · 2025Article
- The TLK-ASF1 histone chaperone pathway plays a critical role in IL-1β-mediated AML progression.Blood · 2024Article
- Article
- Autophosphorylation of the Tousled-like kinases TLK1 and TLK2 regulates recruitment to damaged chromatin via PCNA interaction.bioRxiv : the preprint server for biology · 2024Article
- Review
- Tousled-like kinase 1 promotes gastric cancer progression by regulating the tumor growth factor-beta signaling pathway.World journal of gastroenterology · 2023Article
- TLK1-mediated RAD54 phosphorylation spatio-temporally regulates Homologous Recombination Repair.Nucleic acids research · 2023Article
- Untousling the Role of Tousled-like Kinase 1 in DNA Damage Repair.International journal of molecular sciences · 2023Review
- The Tousled-like kinases regulate genome and epigenome stability: implications in development and disease.Cellular and molecular life sciences : CMLS · 2019Review
- Investigation of the Possible Role of RAD9 in Post-Diapaused Embryonic Development of the Brine ShrimpGenes · 2019Article
- Inactive Tlk associating with Tak1 increases p38 MAPK activity to prolong the G2 phase.Scientific reports · 2019Article
- The circadian E3 ligase complex SCFScientific reports · 2019Article
- TLK2 enhances aggressive phenotypes of glioblastoma cells through the activation of SRC signaling pathway.Cancer biology & therapy · 2019Article
- Conditional genome engineering reveals canonical and divergent roles for the Hus1 component of the 9-1-1 complex in the maintenance of the plastic genome of Leishmania.Nucleic acids research · 2018Article
- Preserving salivary gland physiology against genotoxic damage - the Tousled way.Oral diseases · 2018Review
- Tousled-like kinases stabilize replication forks and show synthetic lethality with checkpoint and PARP inhibitors.Science advances · 2018Article
- Molecular basis of Tousled-Like Kinase 2 activation.Nature communications · 2018Article
- Tousled-like kinase 1 is a negative regulator of core transcription factors in murine embryonic stem cells.Scientific reports · 2018Article
- Loss of miR-16 contributes to tumor progression by activation of tousled-like kinase 1 in oral squamous cell carcinoma.Cell cycle (Georgetown, Tex.) · 2018Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Genomic integrity is preserved by checkpoints, which act to delay cell cycle progression in the presence of DNA damage or replication stress. The heterotrimeric Rad9-Rad1-Hus1 (9-1-1) complex is a PCNA-like clamp that is loaded onto DNA at structures resulting from damage and is important for initiating and maintaining the checkpoint response. Rad9 possesses a C-terminal tail that is phosphorylated constitutively and in response to cell cycle position and DNA damage. Previous studies have identified tousled-like kinase 1 (TLK1) as a kinase that may modify Rad9. Here we show that Rad9 is phosphorylated in a TLK-dependent manner in vitro and in vivo, and that T355 within the C-terminal tail is the primary targeted residue. Phosphorylation of Rad9 at T355 is quickly reduced upon exposure to ionizing radiation before returning to baseline later in the damage response. We also show that TLK1 and Rad9 interact constitutively, and that this interaction is enhanced in chromatin-bound Rad9 at later stages of the damage response. Furthermore, we demonstrate via siRNA-mediated depletion that TLK1 is required for progression through S-phase in normally cycling cells, and that cells lacking TLK1 display a prolonged G2/M arrest upon exposure to ionizing radiation, a phenotype that is mimicked by over-expression of a Rad9-T355A mutant. Given that TLK1 has previously been shown to be transiently inactivated upon phosphorylation by Chk1 in response to DNA damage, we propose that TLK1 and Chk1 act in concert to modulate the phosphorylation status of Rad9, which in turn serves to regulate the DNA damage response.
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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.