Human Tim/Timeless-interacting Protein, Tipin, Is Required for Efficient Progression of S Phase and DNA Replication Checkpoint

• DOI: 10.1074/jbc.m605596200
• Publication Date: 2006-11-14T01:17:48Z
• Authors: Naoko Yoshizawa-S...; Hisao Masai
• Keywords: Timeless; Retinoblastoma protein

Tipin was originally isolated as a protein interacting with Timeless/Tim1/Tim (Tim), which is known to be involved in both circadian rhythm and cell cycle checkpoint regulation. The endogenous Tim proteins human cells, through the N-terminal segment of each molecule, form complex throughout cycle. are expressed interphase nuclei mostly at constant levels during cycle, small fractions recovered chromatin-enriched S phase. Depletion results reduced growth rate, this may due part inefficient progression phase DNA synthesis. Knockdown induces radioresistant synthesis inhibits phosphorylation Chk1 kinase caused by replication stress, observed that Tim. or level relocation cytoplasm respective binding partner, suggesting formation required for stabilization nuclear accumulation proteins. Furthermore, facilitate Claspin under whereas localization unaffected Claspin. Our indicate mammalian mediator cooperates regulate response checkpoint.