TIMELESS
Plays an important role in the control of DNA replication, maintenance of replication fork stability, maintenance of genome stability throughout normal DNA replication, DNA repair and in the regulation of the circadian clock. Required to stabilize replication forks during DNA replication by forming a complex with TIPIN: this complex regulates DNA replication processes under both normal and stress conditions, stabilizes replication forks and influences both CHEK1 phosphorylation and the intra-S phase checkpoint in response to genotoxic stress. TIMELESS promotes TIPIN nuclear localization. Involved in cell survival after DNA damage or replication stress by promoting DNA repair. In response to double-strand breaks (DSBs), accumulates at DNA damage sites and promotes homologous recombination repair via its interaction with PARP1. May be specifically required for the ATR-CHEK1 pathway in the replication checkpoint induced by hydroxyurea or ultraviolet light. Involved in the determination of period length and in the DNA damage-dependent phase advancing of the circadian clock. Negatively regulates CLOCK|NPAS2-ARTNL/BMAL1|ARTNL2/BMAL2-induced transactivation of PER1 possibly via translocation of PER1 into the nucleus. May also play an important role in epithelial cell morphogenesis and formation of branching tubules. Belongs to the timeless family. Expressed in all tissues examined including brain, heart, lung, liver, skeletal muscle, kidney, placenta, pancreas, spleen, thymus and testis. Highest levels of expression in placenta, pancreas, thymus and testis. 2 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
Protein type: Transcription, coactivator/corepressor
Cellular Component: chromatin; nucleoplasm; nucleus; replication fork protection complex; site of double-strand break
Molecular Function: DNA binding; identical protein binding; protein binding
Biological Process: branching morphogenesis of an epithelial tube; cell cycle phase transition; cell division; cellular response to bleomycin; cellular response to cisplatin; cellular response to hydroxyurea; circadian rhythm; detection of abiotic stimulus; DNA damage response; DNA repair; DNA replication checkpoint signaling; lung development; morphogenesis of an epithelium; negative regulation of DNA-templated transcription; positive regulation of double-strand break repair; positive regulation of double-strand break repair via homologous recombination; regulation of cell population proliferation; regulation of circadian rhythm; replication fork arrest