ArticleThe Journal of biological chemistry2009
Timeless Maintains Genomic Stability and Suppresses Sister Chromatid Exchange during Unperturbed DNA Replication.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 40 citations in OpenAlex.
- Intrinsic PARG inhibitor sensitivity is mimicked byNAR cancer · 2024Article
- SP3-induced Timeless transcription contributes to cell growth of lung adenocarcinoma cells.PloS one · 2024Article
- The TIMELESS effort for timely DNA replication and protection.Cellular and molecular life sciences : CMLS · 2023Review
- The Fork Protection Complex: A Regulatory Hub at the Head of the Replisome.Sub-cellular biochemistry · 2022Article
- SDE2 integrates into the TIMELESS-TIPIN complex to protect stalled replication forks.Nature communications · 2020Article
- A Genome-Wide Screen for Genes Affecting Spontaneous Direct-Repeat Recombination inG3 (Bethesda, Md.) · 2020Article
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- Review
- Timeless protection of telomeres.Current genetics · 2016Review
- TIMELESS Forms a Complex with PARP1 Distinct from Its Complex with TIPIN and Plays a Role in the DNA Damage Response.Cell reports · 2015Article
- TIPIN depletion leads to apoptosis in breast cancer cells.Molecular oncology · 2015Article
- Chromatin immunoprecipitation to detect DNA replication and repair factors.Methods in molecular biology (Clifton, N.J.) · 2015Article
- Architecture and ssDNA interaction of the Timeless-Tipin-RPA complex.Nucleic acids research · 2014Article
- BRCA2 prevents R-loop accumulation and associates with TREX-2 mRNA export factor PCID2.Nature · 2014Article
- RNF4 and PLK1 are required for replication fork collapse in ATR-deficient cells.Genes & development · 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
- Timeless preserves telomere length by promoting efficient DNA replication through human telomeres.Cell cycle (Georgetown, Tex.) · 2012Article
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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
Genome integrity is maintained during DNA replication by coordination of various replisome-regulated processes. Although it is known that Timeless (Tim) is a replisome component that participates in replication checkpoint responses to genotoxic stress, its importance for genome maintenance during normal DNA synthesis has not been reported. Here we demonstrate that Tim reduction leads to genomic instability during unperturbed DNA replication, culminating in increased chromatid breaks and translocations (triradials, quadriradials, and fusions). Tim deficiency led to increased H2AX phosphorylation and Rad51 and Rad52 foci formation selectively during DNA synthesis and caused a 3-4-fold increase in sister chromatid exchange. The sister chromatid exchange events stimulated by Tim reduction were largely mediated via a Brca2/Rad51-dependent mechanism and were additively increased by deletion of the Blm helicase. Therefore, Tim deficiency leads to an increased reliance on homologous recombination for proper continuation of DNA synthesis. Together, these results indicate a pivotal role for Tim in maintaining genome stability throughout normal 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.