ArticlePloS one2011
Timeless links replication termination to mitotic kinase activation.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
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The trial behind it
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Who cites it
15 citing papers in PubMed, 23 citations in OpenAlex.
- The TIMELESS effort for timely DNA replication and protection.Cellular and molecular life sciences : CMLS · 2023Review
- Article
- Article
- Overexpression of Claspin and Timeless protects cancer cells from replication stress in a checkpoint-independent manner.Nature communications · 2019Article
- Article
- Chromatin determinants of the inner-centromere rely on replication factors with functions that impart cohesion.Oncotarget · 2016Article
- Analysis of clock gene-miRNA correlation networks reveals candidate drivers in colorectal cancer.Oncotarget · 2016Article
- Viral reprogramming of the Daxx histone H3.3 chaperone during early Epstein-Barr virus infection.Journal of virology · 2014Article
- Linking chromosome duplication and segregation via sister chromatid cohesion.Methods in molecular biology (Clifton, N.J.) · 2014Review
- Potential cancer-related role of circadian gene TIMELESS suggested by expression profiling and in vitro analyses.BMC cancer · 2013Article
- A high resolution genomic portrait of bladder cancer: correlation between genomic aberrations and the DNA damage response.Oncogene · 2013Article
- Timeless-dependent DNA replication-coupled recombination promotes Kaposi's Sarcoma-associated herpesvirus episome maintenance and terminal repeat stability.Journal of virology · 2013Article
- Separation of intra-S checkpoint protein contributions to DNA replication fork protection and genomic stability in normal human fibroblasts.Cell cycle (Georgetown, Tex.) · 2013Article
- Local and global functions of Timeless and Tipin in replication fork protection.Cell cycle (Georgetown, Tex.) · 2012Review
- Telomeres and viruses: common themes of genome maintenance.Frontiers in oncology · 2012Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
The mechanisms that coordinate the termination of DNA replication with progression through mitosis are not completely understood. The human Timeless protein (Tim) associates with S phase replication checkpoint proteins Claspin and Tipin, and plays an important role in maintaining replication fork stability at physical barriers, like centromeres, telomeres and ribosomal DNA repeats, as well as at termination sites. We show here that human Tim can be isolated in a complex with mitotic entry kinases CDK1, Auroras A and B, and Polo-like kinase (Plk1). Plk1 bound Tim directly and colocalized with Tim at a subset of mitotic structures in M phase. Tim depletion caused multiple mitotic defects, including the loss of sister-chromatid cohesion, loss of mitotic spindle architecture, and a failure to exit mitosis. Tim depletion caused a delay in mitotic kinase activity in vivo and in vitro, as well as a reduction in global histone H3 S10 phosphorylation during G2/M phase. Tim was also required for the recruitment of Plk1 to centromeric DNA and formation of catenated DNA structures at human centromere alpha satellite repeats. Taken together, these findings suggest that Tim coordinates mitotic kinase activation with termination of DNA replication.
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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.