FEATURES

FAMILY

DESCRIPTION

Also known as TIM_HUMAN, TIMELESS, TIM, TIM1, TIMELESS1. 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 (PubMed:9856465, PubMed:17141802, PubMed:17296725, PubMed:23418588, PubMed:26344098). 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 (PubMed:17141802, PubMed:17296725). TIMELESS promotes TIPIN nuclear localization (PubMed:17141802, PubMed:17296725). Involved in cell survival after DNA damage or replication stress by promoting DNA repair (PubMed:17141802, PubMed:17296725, PubMed:26344098, PubMed:30356214). In response to double-strand breaks (DSBs), accumulates at DNA damage sites and promotes homologous recombination repair via its interaction with PARP1 (PubMed:26344098, PubMed:30356214). May be specifically required for the ATR-CHEK1 pathway in the replication checkpoint induced by hydroxyurea or ultraviolet light (PubMed:15798197). Involved in the determination of period length and in the DNA damage-dependent phase advancing of the circadian clock (PubMed:23418588). Negatively regulates CLOCK|NPAS2-ARTNL/BMAL1|ARTNL2/BMAL2-induced transactivation of PER1 possibly via translocation of PER1 into the nucleus (PubMed:9856465). May also play an important role in epithelial cell morphogenesis and formation of branching tubules (By similarity). Homodimer or homomultimer (By similarity). Component of the circadian core oscillator, which includes the CRY proteins, CLOCK or NPAS2, ARTNL/BMAL1 or ARTNL2/BMAL2, CSKN1D and/or CSNK1E, TIMELESS, and the PER proteins (PubMed:9856465). Interacts directly with PER2; the interaction with PER2 is via its second PAS domain (By similarity). Interacts directly with PER1 and PER3 (By similarity). Interacts with CRY2, CHEK1, ATR and ATRIP (PubMed:15798197). Interacts with CRY1 (By similarity). Interacts with CLSPN (PubMed:17141802). Interacts with TIPIN (PubMed:17102137, PubMed:17116885, PubMed:17296725). Interacts with DDX11; this interaction increases recruitment of both proteins onto chromatin in response to replication stress induction by hydroxyurea (PubMed:20124417, PubMed:26503245). Interacts with PARP1; interaction is direct and independent of poly-ADP-ribose (PubMed:26344098, PubMed:30356214).

Also known as TIM_HUMAN, TIMELESS, TIM, TIM1, TIMELESS1. Plays an important role in the control of DNA replication, maintenance of replication fork stability, maintenance of genome stability thr ...

EXTERNAL LINKS

TIMELESS

Protein timeless homolog

TIMELESS

Molecular Synopsis