Tumor suppressor stars in yeast G1/S transition

Pan, Li; Hao, Zhimin; Zeng, Fanli

doi:10.1007/s00294-020-01126-3

Cited by 13 publications

(13 citation statements)

References 48 publications

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“…In budding yeast, three G1 cyclins, CLN1, CLN2, and CLN3, are critical for starting the cell cycle and entry into subsequent cell cycle phases (59). These cyclins associate with the cell cycle-dependent kinase Cdc28 in a spatial and temporal manner to regulate the global gene expression.…”

Section: Discussionmentioning

confidence: 99%

S. cerevisiae cells can grow without the Pds5 cohesin subunit

Choudhary

Itzkovich

Alonso-Pérez

et al. 2022

Preprint

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During DNA replication, the newly created sister chromatids are held together until their separation at anaphase. The cohesin complex is in charge of creating and maintaining sister-chromatid cohesion (SCC) in all eukaryotes. In S. cerevisiae cells, cohesin is composed of two elongated proteins, Smc1 and Smc3, bridged by the kleisin Mcd1/Scc1. The latter also acts as a scaffold for three additional proteins, Scc3/Irr1, Wpl1/Rad61, and Pds5. Although the HEAT-repeat protein Pds5 is essential for cohesion, its precise function is still debated. Deletion of the ELG1 gene, encoding a PCNA unloader, can partially suppress the temperature-sensitive pds5-1 allele, but not a complete deletion of PDS5. We carried out a genetic screen for high copy number suppressors and another for spontaneously arising mutants, allowing the survival of a pds5Δ elg1Δ strain. Our results show that cells remain viable in the absence of Pds5 provided that there is both an elevation in the level of Mcd1 (which can be due to mutations in the CLN2 gene, encoding a G1 cyclin), and an increase in the level of SUMO-modified PCNA on chromatin (caused by lack of PCNA unloading in elg1Δ mutants). The elevated SUMO-PCNA levels increase the recruitment of the Srs2 helicase, which evicts Rad51 molecules from the moving fork, creating ssDNA regions that serve as sites for increased cohesin loading and SCC establishment. Thus, our results delineate a double role for Pds5 in protecting the cohesin ring and interacting with the DNA replication machinery.IMPORTANCESister chromatid cohesion is vital for faithful chromosome segregation, chromosome folding into loops, and gene expression. A multisubunit protein complex known as cohesin holds the sister chromatids from S-phase until the anaphase stage. In this study, we explore the function of the essential cohesin subunit Pds5 in the regulation of sister chromatid cohesion. We performed two independent genetic screens to bypass the function of the Pds5 protein. We observe that Pds5 protein is a cohesin stabilizer, and elevating the levels of Mcd1 protein along with SUMO-PCNA accumulation on chromatin can compensate for the loss of the PDS5 gene. In addition, Pds5 plays a role in coordinating the DNA replication and sister chromatid cohesion establishment. This work elucidates the function of cohesin subunit Pds5, the G1 cyclin Cln2, and replication factors PCNA, Elg1 and Srs2 in the proper regulation of sister chromatid cohesion.

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Section: Discussionmentioning

confidence: 99%

S. cerevisiae cells can grow without the Pds5 cohesin subunit

Choudhary

Itzkovich

Alonso-Pérez

et al. 2022

Preprint

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“…G1 cyclins, however, can exert temporal differences in START regulation. For instance, Cln3 in association with cyclin-dependent kinase (Cln3-CDK) is an early inactivator of Whi5 (reviewed Fisher, 2016; Ewald, 2018; Li et al, 2021). Whi5, the yeast homolog of human retinoblastoma protein (Crane et al, 2019), is an inhibitor of the SBF-dependent transcription of genes that are required for the transition into S phase (Talerak et al, 2017; Teufel et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

G1-Cyclin2 (Cln2) promotes chromosome hypercondensation in eco1/ctf7 rad61 null cells during hyperthermic stress in Saccharomyces cerevisiae

Buskirk

Skibbens

2022

Preprint

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Eco1/Ctf7 is a highly conserved acetyltransferase that activates cohesin complexes and is critical for sister chromatid cohesion, chromosome condensation, DNA damage repair, nucleolar integrity, and gene transcription. Mutations in the human homolog of ECO1 (ESCO2/EFO2), or in genes that encode cohesin subunits, result in severe developmental abnormalities and intellectual disabilities referred to as Roberts Syndrome (RBS) and Cornelia de Lange Syndrome (CdLS), respectively. In yeast, deletion of ECO1 results in cell inviability. Co-deletion of RAD61 (WAPL in humans), however, produces viable yeast cells. These eco1 rad61 double mutants, however, exhibit a severe temperature-sensitive growth defect, suggesting that Eco1 or cohesins respond to hyperthermic stress through a mechanism that occurs independent of Rad61. Here, we report that deletion of the G1 cyclin CLN2 rescues the temperature sensitive lethality otherwise exhibited by eco1 rad61 mutant cells, such that the triple mutant cells exhibit robust growth over a broad range of temperatures. While Cln1, Cln2 and Cln3 are functionally redundant G1 cyclins, neither CLN1 nor CLN3 deletions rescue the temperature-sensitive growth defects otherwise exhibited by eco1 rad61 double mutants. We further provide evidence that CLN2 deletion rescues hyperthermic growth defects independent of START and impacts the state of chromosome condensation. These findings reveal novel roles for Cln2 that are unique among the G1 cyclin family and appear critical for cohesin regulation during hyperthermic stress.

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“…Maize growth and infection were as described previously (Zeng et al, 2020 ). The yeast YTK12 strain was routinely grown on YPD medium (1% yeast, 2% peptone, 2% glucose, and 2% agar) at 30℃, and the yeast genetic manipulations followed standard procedures (Li et al, 2020a , 2020b ; Liu et al, 2020 ). Agrobacterium tumefaciens GV3101 was used for Agrobacterium ‐mediated transient gene expression in plant leaves.…”

Section: Methodsmentioning

confidence: 99%

Novel factors contributing to fungal pathogenicity at early stages of Setosphaeria turcica infection

Meng

Zeng

et al. 2021

Molecular Plant Pathology

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Setosphaeria turcica is the causal agent of northern corn leaf blight, which is one of the most important maize foliar diseases (Cao et al., 2020;Perkins & Pedercens, 1987;Van Inghelandt et al., 2012). Early infection starts when a conidium of S. turcica lands on the maize leaf surface and germinates to form a highly polarized germ tube.The germ tube elongates and becomes flattened against the plant

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Tumor suppressor stars in yeast G1/S transition

Cited by 13 publications

References 48 publications

S. cerevisiae cells can grow without the Pds5 cohesin subunit

S. cerevisiae cells can grow without the Pds5 cohesin subunit

G1-Cyclin2 (Cln2) promotes chromosome hypercondensation in eco1/ctf7 rad61 null cells during hyperthermic stress in Saccharomyces cerevisiae

Novel factors contributing to fungal pathogenicity at early stages of Setosphaeria turcica infection

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