Michelle Trickey

University College London

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Field

Hsk1- and SCFPof3-Dependent Proteolysis of S. pombe Ams2 Ensures Histone Homeostasis and Centromere Function

Developmental Cell (2010)

Yuko Takayama Yasmine M. Mamnun Michelle Trickey Susheela Dhut Fumie Masuda

Schizosaccharomyces pombe GATA factor Ams2 is responsible for cell cycle-dependent transcriptional activation of all the core histone genes peaking at G1/S phase. Intriguingly, its own protein level also fluctuates concurrently. Here, we show that Ams2 is ubiquitylated and degraded through the SCF (Skp1-Cdc53/Cullin-1-F-box) ubiquitin ligase, in which F box protein Pof3 binds this protein. Ams2 is phosphorylated at multiple sites, which is required for SCF(Pof3)-dependent proteolysis. Hsk1/Cdc7 kinase physically associates with and phosphorylates Ams2. Even mild overexpression of Ams2 induces constitutive histone expression and chromosome instability, and its toxicity is exaggerated when Hsk1 function is compromised. This is partly attributable to abnormal incorporation of canonical H3 into the central CENP-A/Cnp1-rich centromere, thereby reversing specific chromatin structures to apparently normal nucleosomes. We propose that Hsk1 plays a vital role during post S phase in genome stability via SCF(Pof3)-mediated degradation of Ams2, thereby maintaining centromere integrity.

Cullin

Proteolysis

F-box protein

10.1016/j.devcel.2009.12.024

Cite

Citations (38)

A Proteome-wide Fission Yeast Interactome Reveals Network Evolution Principles from Yeasts to Human

Cell (2016)

Tommy V. Vo Jishnu Das Michael J. Meyer Nicolas A. Cordero Nurten Akturk

Interactome

Proteome

Schizosaccharomyces

Human proteome project

10.1016/j.cell.2015.11.037

Cite

Citations (120)

The Anaphase-Promoting Complex/Cyclosome Controls Repair and Recombination by Ubiquitylating Rhp54 in Fission Yeast

Molecular and Cellular Biology (2008)

Michelle Trickey Margaret Grimaldi Hiroyuki Yamano

Homologous recombination (HR) is important for maintaining genome integrity and for the process of meiotic chromosome segregation and the generation of variation.HR is regulated throughout the cell cycle, being prevalent in the S and G 2 phases and suppressed in the G 1 phase.Here we show that the anaphasepromoting complex/cyclosome (APC/C) regulates homologous recombination in the fission yeast Schizosaccharomyces pombe by ubiquitylating Rhp54 (an ortholog of Rad54).We show that Rhp54 is a novel APC/C substrate that is destroyed in G 1 phase in a KEN-box-and Ste9/Fizzy-related manner.The biological consequences of failing to temporally regulate HR via Rhp54 degradation are seen in haploid cells only in the absence of antirecombinase Srs2 function and are more extensive in diploid cells, which become sensitive to a range of DNA-damaging agents, including hydroxyurea, methyl methanesulfonate, bleomycin, and UV.During meiosis, expression of nondegradable Rhp54 inhibits interhomolog recombination and stimulates sister chromatid recombination.We thus propose that it is critical to control levels of Rhp54 in G 1 to suppress HR repair of double-strand breaks and during meiosis to coordinate interhomolog recombination.

FLP-FRT recombination

Synaptonemal complex

Methyl methanesulfonate

Mitotic crossover

Schizosaccharomyces

10.1128/mcb.02116-07

Cite

Citations (23)

APC/C‐dependent degradation of Spd2 regulates centrosome asymmetry in Drosophila neural stem cells

EMBO Reports (2023)

Francesco Meghini Torcato Martins Zhang Qian Nicolas Loyer Michelle Trickey

Abstract A functional centrosome is vital for the development and physiology of animals. Among numerous regulatory mechanisms of the centrosome, ubiquitin‐mediated proteolysis is known to be critical for the precise regulation of centriole duplication. However, its significance beyond centrosome copy number control remains unclear. Using an in vitro screen for centrosomal substrates of the APC/C ubiquitin ligase in Drosophila , we identify several conserved pericentriolar material (PCM) components, including the inner PCM protein Spd2. We show that Spd2 levels are controlled by the interphase‐specific form of APC/C, APC/C Fzr , in cultured cells and developing brains. Increased Spd2 levels compromise neural stem cell–specific asymmetric PCM recruitment and microtubule nucleation at interphase centrosomes, resulting in partial randomisation of the division axis and segregation patterns of the daughter centrosome in the following mitosis. We further provide evidence that APC/C Fzr ‐dependent Spd2 degradation restricts the amount and mobility of Spd2 at the daughter centrosome, thereby facilitating the accumulation of Polo‐dependent Spd2 phosphorylation for PCM recruitment. Our study underpins the critical role of cell cycle–dependent proteolytic regulation of the PCM in stem cells.

Centrosome cycle

Centriole

10.15252/embr.202255607

Cite

Citations (4)

In Vitro Assays for the Anaphase-Promoting Complex/Cyclosome (APC/C) in Xenopus Egg Extracts

Methods in molecular biology (2009)

Hiroyuki Yamano Michelle Trickey Margaret Grimaldi Yuu Kimata

Proteolysis

Anaphase-promoting complex

10.1007/978-1-60327-993-2_18

Cite

Citations (13)

The role of Schizosaccharomyces pombe SUMO ligases in genome stability

Biochemical Society Transactions (2007)

Felicity Z. Watts Andrew Skilton Jenny Ho Lara K. Boyd Michelle Trickey

SUMOylation is a post-translational modification that affects a large number of proteins, many of which are nuclear. While the role of SUMOylation is beginning to be elucidated, it is clear that understanding the mechanisms that regulate the process is likely to be important. Control of the levels of SUMOylation is brought about through a balance of conjugating and deconjugating activities, i.e. of SUMO (small ubiquitin-related modifier) conjugators and ligases versus SUMO proteases. Although conjugation of SUMO to proteins can occur in the absence of a SUMO ligase, it is apparent that SUMO ligases facilitate the SUMOylation of specific subsets of proteins. Two SUMO ligases in Schizosaccharomyces pombe, Pli1 and Nse2, have been identified, both of which have roles in genome stability. We report here on a comparison between the properties of the two proteins and discuss potential roles for the proteins.

SUMO enzymes

Schizosaccharomyces

10.1042/bst0351379

Cite

Citations (36)

Anaphase-promoting Complex/Cyclosome-mediated Proteolysis of Ams2 in the G1 Phase Ensures the Coupling of Histone Gene Expression to DNA Replication in Fission Yeast

Journal of Biological Chemistry (2012)

Michelle Trickey Kazuyuki Fujimitsu Hiroyuki Yamano

Replication factor C

10.1074/jbc.m112.410241

Cite

Citations (11)