High impact information on CDC40

• Furthermore, the absence of a functional Xrs2p complex leads to sensitivity to deoxynucleotide depletion and to an inability to efficiently slow down cell cycle progression in response to hydroxyurea [1].
• This suggests that SLU7 is involved in the process of 3' splice site choice, whereas SLU4 fulfills a generic requirement for the second step [2].
• Here, we show that MRX (Mre11-Rad50-Xrs2), an evolutionarily conserved protein complex involved in DNA double-strand break (DSB) repair, is recruited to the telomeres in late S phase [3].
• Although SLU7 encodes an essential gene product, we find that a null allele of prp17 is temperature-sensitive for growth and has a partial splicing defect in vitro [4].
• While most of these genes are essential for yeast mating-type (MAT) gene switching, neither RAD50 nor XRS2 is required to complete this specialized mitotic gene conversion process [5].

Biological context of CDC40

• It was found recently that PRP17 is identical to the cell division cycle CDC40 gene. cdc40 mutants arrest at the restrictive temperature after the completion of DNA replication [6].
• Saccharomyces cerevisiae PRP17 (CDC40) encodes a second-step pre-mRNA splicing factor with a role in cell division [7].
• The PRP17/CDC40 gene of Saccharomyces cerevisiae functions in two different cellular processes: pre-mRNA splicing and cell cycle progression [8].
• We show that mutations in the PRP8 gene are able to suppress the temperature-sensitive growth phenotype and the splicing defect conferred by the absence of the Prp17 protein [6].
• Dependence of pre-mRNA introns on PRP17, a non-essential splicing factor: implications for efficient progression through cell cycle transitions [7].

Anatomical context of CDC40

• Using immunofluorescence, we show that Cdc40p is localized to the nuclear membrane, weakly associated with the nuclear pore [9].

Associations of CDC40 with chemical compounds

• RAD6 mRNA levels increase when cells are treated with MMS, but this increase seems to be due to the arrest of the cells by MMS at the repair-specific stage; cells arrested at the same stage by HU or by the cdc40 lesion also show high levels of RAD6 mRNA [10].
• This stage is the one at which rad6 mutants arrest, as do wild-type cells exposed to hydroxyurea (HU) or methyl methanesulfonate (MMS), or cdc40 cells exposed to the restrictive temperature [10].
• We screened a cDNA overexpression library and isolated cDNAs that specifically suppress the HU/MMS-sensitivity of cdc40 mutants [11].

Physical interactions of CDC40

• We therefore suggest that the functional region of Prp17p that interacts with Prp18p, Prp16p, and U5 snRNA is the N terminal region of the protein [12].

Regulatory relationships of CDC40

• The Saccharomyces cerevisiae gene CDC40/PRP17 controls cell cycle progression through splicing of the ANC1 gene [13].

Other interactions of CDC40

• Moreover, other PRP8 alleles exhibit synthetic lethality with the absence of Prp17p and show a reduced ability to splice an intron bearing an altered 3' splice junction [6].
• Interestingly, deletion of SKY1 was synthetically lethal with all prp17 mutants tested, but only with specific prp8 alleles in a domain implicated in governing fidelity of 3'AG recognition [14].
• Genomic replacement of an intronless TUB1 gene relieves the benomyl sensitivity of prp17 mutants; however, they remain temperature sensitive, implying multiple limiting factors for mitosis [7].
• In vitro splicing with TUB3 pre-mRNA demonstrates a compromised second step in prp17::LEU2 extracts, implicating a direct role for Prp17 in its efficient splicing [7].
• Only mutations in the N-terminal nonconserved domain of PRP17 are synthetically lethal in combination with mutations in PRP16 and PRP18, two other gene products required for the second splicing reaction [12].

Analytical, diagnostic and therapeutic context of CDC40

• Sequence analysis reveals that CDC40 is identical to PRP17, a gene involved in pre-mRNA splicing [9].
• Quantitative polymerase chain reactions confirm the array-based finding that Prp17p and Prp18p are not dispensable for removal of introns with short branchpoint-to-3' splice site distances [15].

References