Characterization of the SAC3 gene of Saccharomyces cerevisiae

Bauer, Andreas; Kölling, Ralf

doi:10.1002/(sici)1097-0061(199608)12:10<965::aid-yea999>3.0.co;2-q

Cited by 22 publications

(16 citation statements)

References 22 publications

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“…2B). This is consistent with a loss of function phenotype previously reported for SAC3 (16). As a complementary experiment, we examined the effect of overexpressing the Sac3 protein from a galactose-inducible promoter.…”

Section: Alterations In the Level Of Sac3p Expression Affect Mitotic supporting

confidence: 84%

“…Complementation of the synthetic lethal phenotype in conjunction with genetic linkage analysis revealed that three of the mutations were in the SAC3, SDS23, and CDC28 genes. The function of SAC3 has not been delineated, but it was identified first as a suppressor of actin (36) and subsequently implicated in mitotic regulation (16). The SDS23 gene encodes one of two S. cerevisiae homologues (Ssd23p and Sds24p) of the fission yeast Sds23 protein, which genetic studies have implicated in APC͞ cyclosome regulation (37).…”

Section: Identification Of Sac3mentioning

confidence: 99%

“…We report here the identification of a nuclear export factor, Sac3p, a protein that previously has been implicated in control of mitosis (16). We identified the S. cerevisiae SAC3 gene in two complementary genetic screens for regulators of mitosis.…”

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confidence: 99%

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SAC3 may link nuclear protein export to cell cycle progression

Jones¹

2000

Proceedings of the National Academy of Sciences

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Selective movement of proteins between the nucleus and the cytoplasm is a regulatory mechanism exploited extensively by the eukaryotic cell. We have identified the evolutionarily conserved Sac3 protein, which was implicated previously in the regulation of mitosis [Bauer, A. & Kö lling, R. (1996) J. Cell Sci. 109, 1575-1583] as a novel mediator of nuclear protein export. We show that Sac3p is localized to the nuclear pore, where it interacts with nucleoporins. Loss of SAC3 function results in a block in nuclear export of a nuclear export signal-containing reporter protein. Our results also demonstrate that SAC3 interacts genetically with the nuclear protein export factors Crm1p͞Xpo1p and Yrb2p. Taken together, these data indicate a link between nuclear protein export and transition through the cell cycle. The nuclear envelope provides a physical mechanism for regulation of numerous events in the eukaryotic cell. The segregation of essential cellular processes such as transcription and translation conferred by the separation of the nucleus and the cytoplasm allows cells to use compartmentalization as a method for controlling critical cellular processes. Efficient use of this regulatory mechanism requires rapid but highly regulated pathways for exchange of information between the nucleus and the cytoplasm. The route for this exchange in all cells is via nuclear pore complexes that form large proteinaceous channels in the double membrane that surrounds the nucleus (1). In addition to the nuclear pore proteins, which are called nucleoporins, a growing number of soluble factors are required to escort substrates through the nuclear pore complex (2). These factors can be divided into two general classes: those that target substrates to the nuclear pore, including the soluble receptors of the importin family (3), and those that are required for the actual translocation through the pore, primarily the small, GTPbinding protein Ran and its binding partner NTF2 (4, 5).For many years, studies have focused on how entry of proteins into the nucleus can regulate cellular responses to external stimuli. Several recent developments have led researchers to consider the potential impact of selective export of proteins from the nucleus. Approximately 5 years ago, a nuclear export signal (NES) that targets substrate proteins for export from the nucleus was defined (6). This discovery was followed rapidly by the identification of an NES receptor called Xpo1p͞Crm1p in Saccharomyces cerevisiae (7,8) and CRM1 in other eukaryotes (9). The nuclear export receptor is a member of a large family of proteins related to the importin ␤-subunit of the classical nuclear localization signal (NLS) receptor. Despite these recent advances, the mechanism of nuclear protein export is not understood in detail. Thus far, only one additional soluble factor has been implicated in the process, the Ran-binding protein Yrb2p (10,11).Interest in the detailed mechanism of nuclear protein export has been sparked further by several recent studies that demonstrate t...

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Section: Alterations In the Level Of Sac3p Expression Affect Mitotic supporting

confidence: 84%

Section: Identification Of Sac3mentioning

confidence: 99%

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SAC3 may link nuclear protein export to cell cycle progression

Jones¹

2000

Proceedings of the National Academy of Sciences

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“…It may be that these ORFs act in part to arrest cell cycle progression when the appropriate checkpoint pathway is induced. ⌬yil036w was found to be benomyl resistant, a phenotype often associated with a direct or indirect role in microtubule function and cell cycle control (21,22).…”

Section: Resultsmentioning

confidence: 99%

A large-scale overexpression screen in Saccharomyces cerevisiae identifies previously uncharacterized cell cycle genes

Stevenson

Kennedy

Harlow

2001

Proc. Natl. Acad. Sci. U.S.A.

109

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We have undertaken an extensive screen to identify Saccharomyces cerevisiae genes whose products are involved in cell cycle progression. We report the identification of 113 genes, including 19 hypothetical ORFs, which confer arrest or delay in specific compartments of the cell cycle when overexpressed. The collection of genes identified by this screen overlaps with those identified in loss-of-function cdc screens but also includes genes whose products have not previously been implicated in cell cycle control. Through analysis of strains lacking these hypothetical ORFs, we have identified a variety of new CDC and checkpoint genes.C ell cycle studies performed with Saccharomyces cerevisiae have served as a guideline for understanding eukaryotic cell cycle progression. In particular, the now classic screens by Hartwell and colleagues (1-6) to identify temperature-sensitive mutants with specific arrest points throughout the cell division cycle (cdc) have shed light on numerous aspects of cell cycle, including progression through START (e.g., CDC28), regulation of DNA replication (e.g., CDC6), and control of mitosis (e.g., CDC14).Although the cumulative cdc screens performed to date have been extensive, Hartwell and colleagues proposed that there may be additional CDC genes that are difficult or impossible to uncover by using a recessive loss-of-function approach (6). Reasons for this difficulty were speculated to include: (i) a lack of susceptibility of the gene product to generation of a temperature-sensitive allele; (ii) the presence in the genome of a closely related gene with similar or redundant function (e.g., cyclins); (iii) the presence of CDC genes that are helpful but not absolutely required for cell cycle progression; and (iv) the assumption of a morphologically homogeneous terminal phenotype for all cdc mutants (6). In addition, it has since become apparent that protein degradation during the cell cycle is a highly regulated process that contributes to many stages of cell cycle progression. A change in turnover of some encoded gene products can lead to cell cycle arrest (7-9). Such genes would likely escape detection in the cdc screens.In an effort to complement the original cdc screens and in the interest of uncovering new CDC genes from within the categories described above, we undertook an extensive overexpression screen to identify genes that cause an alteration in cell cycle progression. By using this approach, we expected to uncover genes whose overexpression leads to hypermorphic, antimorphic, or neomorphic effects. Many of these genes should be involved at some level in the yeast cell cycle. To further delineate these putative cell cycle genes, we analyzed all of the initial positives by a variety of other assays to establish their roles in cell cycle control.We used a conditional overexpression approach with a S. cerevisiae cDNA library under control of the GAL1 promoter (10). A second smaller screen was performed by using a sheared genomic library under GAL1 control (11). Several previous studi...

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“…A potential explanation for the suppression of act1-1 by sac3 Ϫ mutants is that diminished export of the defective actin transcript decreases the deleterious effects of this actin mutation. However, this possibility is unlikely because the suppression is allele specific (Bauer and Kö lling, 1996a;Novick et al, 1989), suggesting that loss of SAC3 function does not bypass the act1-1 mutation. In addition, a later study found that mutation of SAC3 causes aberrant mitosis and spindle morphology (Bauer and Kö lling, 1996b).…”

Section: Discussionmentioning

confidence: 99%

Sac3 Is an mRNA Export Factor That Localizes to Cytoplasmic Fibrils of Nuclear Pore Complex

Lei

Stern

Fahrenkrog

et al. 2003

MBoC

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In eukaryotes, mRNAs are transcribed in the nucleus and exported to the cytoplasm for translation to occur. Messenger RNAs complexed with proteins referred to as ribonucleoparticles are recognized for nuclear export in part by association with Mex67, a keySaccharomyces cerevisiae mRNA export factor and homolog of human TAP/NXF1. Mex67, along with its cofactor Mtr2, is thought to promote ribonucleoparticle translocation by interacting directly with components of the nuclear pore complex (NPC). Herein, we show that the nuclear pore-associated protein Sac3 functions in mRNA export. Using a mutant allele of MTR2 as a starting point, we have identified a mutation in SAC3 in a screen for synthetic lethal interactors. Loss of function of SAC3 causes a strong nuclear accumulation of mRNA and synthetic lethality with a number of mRNA export mutants. Furthermore, Sac3 can be coimmunoprecipitated with Mex67, Mtr2, and other factors involved in mRNA export. Immunoelectron microscopy analysis shows that Sac3 localizes exclusively to cytoplasmic fibrils of the NPC. Finally, Mex67 accumulates at the nuclear rim when SAC3 is mutated, suggesting that Sac3 functions in Mex67 translocation through the NPC.

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Characterization of the SAC3 gene of Saccharomyces cerevisiae

Cited by 22 publications

References 22 publications

SAC3 may link nuclear protein export to cell cycle progression

SAC3 may link nuclear protein export to cell cycle progression

A large-scale overexpression screen in Saccharomyces cerevisiae identifies previously uncharacterized cell cycle genes

Sac3 Is an mRNA Export Factor That Localizes to Cytoplasmic Fibrils of Nuclear Pore Complex

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