Timeless circadian regulator (TIMELESS) (TIMELESS)

The Timeless circadian regulator (TIMELESS) is a highly conserved protein that plays a dual role in coordinating the circadian clock and maintaining genomic integrity during DNA replication. It interacts with the TIMELESS-interacting protein (TIPIN) to form a complex that associates with the replisome, where it stabilizes replication forks and ensures efficient DNA synthesis, particularly under conditions of replication stress [1, 3]. Beyond its role in the S-phase checkpoint and DNA damage response, TIMELESS is a core component of the mammalian circadian oscillator, helping to regulate the timing of physiological processes [1, 4]. In many human malignancies, TIMELESS is significantly overexpressed and correlates with advanced tumor stage, poor prognosis, and resistance to platinum-based chemotherapies [2, 4]. Consequently, it has emerged as a compelling therapeutic target; inhibiting TIMELESS via antisense oligonucleotides or small molecules can disrupt replication fork stability and sensitize cancer cells to DNA-damaging agents [4]. Sources: [1] UniProt Consortium. "Timeless circadian regulator (Human)." Q9UNS1. [2] Chi, L., et al. "TIMELESS: A potential oncogene and therapeutic target in cancer." (2018). [3] Leman, A. R., & Noguchi, E. "The replication fork: understanding the eukaryotic replication machinery and the challenges to genome stability." (2013). [4] Zhang, Y., et al. "The role of TIMELESS in cancer: from mechanism to therapy." (2021).

Other names

TIMTMLTimeless homologhTIM

Antisense-mediated mRNA degradation leading to reduced protein expression; disruption of the TIMELESS-TIPIN complex to induce replication fork collapse.