High impact information on chk1

• Fission yeast chk1 protein kinase links the rad checkpoint pathway to cdc2 [1].
• Cdc25 mitotic inducer targeted by chk1 DNA damage checkpoint kinase [2].
• Dis2 abrogates Chk1 phosphorylation and activation in vivo, and dephosphorylates Chk1 and a phospho-S345 Chk1 peptide in vitro. dis2Delta cells have a prolonged chk1-dependent arrest and a compromised ability to downregulate Chk1 activity for checkpoint release [3].
• Further, wee1 is required for cell cycle arrest induced by up-regulation of an essential component of this checkpoint, chk1 [4].
• In a search for Schizosaccharomyces pombe mutants that abolish the S phase cell cycle arrest of a thermosensitive DNA polymerase delta strain at 37 degrees C, we isolated two chk1 alleles [5].

Biological context of chk1

• We show that strains carrying any of these mutations enter lethal mitosis in the absence of the radiation checkpoint chk1/rad27 [6].
• The upstream signal transduction pathways involved in the G2 arrest following ionizing radiation remain obscure in mammalian cells; however, in the budding yeast the rad9 gene and in the fission yeast the chk1/rad27 gene are involved [7].
• Of 44 chk1 mutants recovered, six encode full-length proteins that confer a DNA damage-sensitive phenotype [8].
• To further characterize the behavior of Chk1 in response to DNA damage, we used PCR-based mutagenesis of the chk1 gene coupled with in vivo gap repair to generate mutant alleles [8].
• Induction of chk1 enhanced the survival of an A-T cell line in response to radiation exposure as determined by cell viability and reduction of radiation-induced chromosome aberrations [9].

Other interactions of chk1

• High levels of Spd1p lead to an increase in Y15 phosphorylation of Cdc2p and we show that the block over G(2) requires the Wee1p kinase and is dependent on the rad and chk1/cds1 checkpoint genes [10].

References