The timeless gene in Drosophila melanogasteris involved in circadian rhythm control []. Drosophila contains two paralogs, dTIM and dTIM2, acting in clock/photoreception and chromosome integrity/photoreception respectively. The mammalian TIMELESS (TIM) protein, originally identified based on its similarity to Drosophila dTIM, interacts with the clock proteins dCRY and dPER and is essential for circadian rhythm generation and photo-entrainment in the fly []. However, phylogenetic sequence analysis has demonstrated that dTIM2 is likely to be the orthologue of mammalian TIM and other widely conserved TIM-like proteins in eukaryotes []. These proteins include Saccharomyces cerevisiae Tof1, Schizosaccharomyces pombe Swi1, and Caenorhabditis elegans TIM. These proteins are not involved in the core clock mechanism, but instead play important roles in chromosome integrity, efficient cell growth and/or development [, ], with the exception of dTIM-2, that has an additional function in retinal photoreception [].Saccharomyces cerevisiae Tof1 is a subunit of a replication-pausing checkpoint complex (Tof1-Mrc1-Csm3) that acts at the stalled replication fork to promote sister chromatid cohesion after DNA damage, facilitating gap repair of damaged DNA [, ]. Schizosaccharomyces pombe Swi1 and Swi3 form the fork protection complex that coordinates leading- and lagging-strand synthesis and stabilizes stalled replication forks []. In humans timeless forms a stable complex with its partner protein Tipin. The Timeless-Tipin complex has been reported to travel along with the replication fork during unperturbed DNA replication. Moreover, the Timeless-Tipin-Claspin complex contributes to full activation of the ATR-Chk1 signaling pathway through the recruitment of Chk1 to arrested replication forks for sufficient ATR-mediated phosphorylation. It also interacts with PARP-1, and this interaction is required for efficient homologous recombination repair [].
This entry represents the N-terminal domain of the Timeless protein. The timeless gene in Drosophila melanogasteris involved in circadian rhythm control []. Drosophila contains two paralogs, dTIM and dTIM2, acting in clock/photoreception and chromosome integrity/photoreception respectively. The mammalian TIMELESS (TIM) protein, originally identified based on its similarity to Drosophila dTIM, interacts with the clock proteins dCRY and dPER and is essential for circadian rhythm generation and photo-entrainment in the fly []. However, phylogenetic sequence analysis has demonstrated that dTIM2 is likely to be the orthologue of mammalian TIM and other widely conserved TIM-like proteins in eukaryotes []. These proteins include Saccharomyces cerevisiae Tof1, Schizosaccharomyces pombe Swi1, and Caenorhabditis elegans TIM. These proteins are not involved in the core clock mechanism, but instead play important roles in chromosome integrity, efficient cell growth and/or development [, ], with the exception of dTIM-2, that has an additional function in retinal photoreception [].Saccharomyces cerevisiae Tof1 is a subunit of a replication-pausing checkpoint complex (Tof1-Mrc1-Csm3) that acts at the stalled replication fork to promote sister chromatid cohesion after DNA damage, facilitating gap repair of damaged DNA [, ]. Schizosaccharomyces pombe Swi1 and Swi3 form the fork protection complex that coordinates leading- and lagging-strand synthesis and stabilizes stalled replication forks []. In humans timeless forms a stable complex with its partner protein Tipin. The Timeless-Tipin complex has been reported to travel along with the replication fork during unperturbed DNA replication. Moreover, the Timeless-Tipin-Claspin complex contributes to full activation of the ATR-Chk1 signaling pathway through the recruitment of Chk1 to arrested replication forks for sufficient ATR-mediated phosphorylation. It also interacts with PARP-1, and this interaction is required for efficient homologous recombination repair [].
This entry represents the C-terminal domain found in the Timeless (TIM) proteins. This domain can be found in TIM homologues mostly from animals. This domain found in hTIM has been shown to bind to the PARP-1 catalytic domain [].The timeless gene in Drosophila melanogasteris involved in circadian rhythm control []. Drosophila contains two paralogs, dTIM and dTIM2, acting in clock/photoreception and chromosome integrity/photoreception respectively. The mammalian TIMELESS (TIM) protein, originally identified based on its similarity to Drosophila dTIM, interacts with the clock proteins dCRY and dPER and is essential for circadian rhythm generation and photo-entrainment in the fly []. However, phylogenetic sequence analysis has demonstrated that dTIM2 is likely to be the orthologue of mammalian TIM and other widely conserved TIM-like proteins in eukaryotes []. These proteins include Saccharomyces cerevisiae Tof1, Schizosaccharomyces pombe Swi1, and Caenorhabditis elegans TIM. These proteins are not involved in the core clock mechanism, but instead play important roles in chromosome integrity, efficient cell growth and/or development [, ], with the exception of dTIM-2, that has an additional function in retinal photoreception [].Saccharomyces cerevisiae Tof1 is a subunit of a replication-pausing checkpoint complex (Tof1-Mrc1-Csm3) that acts at the stalled replication fork to promote sister chromatid cohesion after DNA damage, facilitating gap repair of damaged DNA [, ]. Schizosaccharomyces pombe Swi1 and Swi3 form the fork protection complex that coordinates leading- and lagging-strand synthesis and stabilizes stalled replication forks []. In humans timeless forms a stable complex with its partner protein Tipin. The Timeless-Tipin complex has been reported to travel along with the replication fork during unperturbed DNA replication. Moreover, the Timeless-Tipin-Claspin complex contributes to full activation of the ATR-Chk1 signaling pathway through the recruitment of Chk1 to arrested replication forks for sufficient ATR-mediated phosphorylation. It also interacts with PARP-1, and this interaction is required for efficient homologous recombination repair [].
Proteins in this family contain a domain found in yeast chromosome segregation in meiosis protein 3. Proteins include:Chromosome segregation in meiosis protein 3, which is required for required for chromosome segregation during meiosis and DNA damage repair, forming a fork protection complex with TOF1 [, ].TIMELESS-interacting protein (also known as TIPIN), which is a nuclear protein that associates with the replicative helicase, and is required for efficient cell cycle arrest in response to DNA damage. It forms a checkpoint complex with TIMELESS []. Protein TIPIN homolog, which is the orthologue of TIPIN from Caenorhabditis elegans and Drosophila melanogaster.Swi1-interacting protein swi3, from Schizosaccharomyces pombe, which forms a fork protection complex with swi1 [].
