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Woolstencroft RN, et al.  (2006) Ccr4 contributes to tolerance of replication stress through control of CRT1 mRNA poly(A) tail length. J Cell Sci 119(Pt 24):5178-92

Abstract: In Saccharomyces cerevisiae, DNA replication stress activates the replication checkpoint, which slows S-phase progression, stabilizes slowed or stalled replication forks, and relieves inhibition of the ribonucleotide reductase (RNR) complex. To identify novel genes that promote cellular viability after replication stress, the S. cerevisiae non-essential haploid gene deletion set (4812 strains) was screened for sensitivity to the RNR inhibitor hydroxyurea (HU). Strains bearing deletions in either CCR4 or CAF1/POP2, which encode components of the cytoplasmic mRNA deadenylase complex, were particularly sensitive to HU. We found that Ccr4 cooperated with the Dun1 branch of the replication checkpoint, such that ccr4Delta dun1Delta strains exhibited irreversible hypersensitivity to HU and persistent activation of Rad53. Moreover, because ccr4Delta and chk1Delta exhibited epistasis in several genetic contexts, we infer that Ccr4 and Chk1 act in the same pathway to overcome replication stress. A counterscreen for suppressors of ccr4Delta HU sensitivity uncovered mutations in CRT1, which encodes the transcriptional repressor of the DNA-damage-induced gene regulon. Whereas Dun1 is known to inhibit Crt1 repressor activity, we found that Ccr4 regulates CRT1 mRNA poly(A) tail length and may subtly influence Crt1 protein abundance. Simultaneous overexpression of RNR2, RNR3 and RNR4 partially rescued the HU hypersensitivity of a ccr4Delta dun1Delta strain, consistent with the notion that the RNR genes are key targets of Crt1. These results implicate the coordinated regulation of Crt1 via Ccr4 and Dun1 as a crucial nodal point in the response to DNA replication stress.

Status: Published Type: Journal Article PubMed ID: 17158920

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Topics Topics not linked to Genes Genes linked to topics (#1 - 10 )
AKR1 CCR4 CDC40 CHK1 CIK1 CTF4 DCC1 DIA2 DUN1 ELG1
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Topics Genes linked to topics (#11 - 20 )
GRR1 HFI1 KAR3 MEC1 MET18 MMS22 MMS4 MRC1 MRE11 MTQ2
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Topics Genes linked to topics (#21 - 30 )
MUS81 PAN2 PAT1 PBP1 PBY1 PHO85 POL32 POP2 PRI1 PTC1
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Topics Genes linked to topics (#31 - 40 )
RAD27 RAD5 RAD50 RAD51 RAD52 RAD53 RAD54 RAD55 RAD57 RAD59
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Topics Genes linked to topics (#41 - 50 )
RFX1 RNR1 RNR2 RNR3 RNR4 ROX3 RTT107 RVS161 SGS1 SML1
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Topics Genes linked to topics (#51 - 60 )
SNF2 SOD1 SRB2 SRB5 TEL1 TOP3 XRS2 YGL024W YLR235C YNL171C
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Topics Genes linked to topics (#61 - 62 )
YPK1 YPR099C
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