Related Experiment Video

Updated: Jun 15, 2026

Single-molecule Imaging of Gene Regulation In vivo Using Cotranslational Activation by Cleavage (CoTrAC)
11:31

Single-molecule Imaging of Gene Regulation In vivo Using Cotranslational Activation by Cleavage (CoTrAC)

Published on: March 15, 2013

Transformation/transcription domain-associated protein (TRRAP)-mediated regulation of Wee1

Teresa M Calonge1, Majid Eshaghi, Jianhua Liu

  • 1Department of Oncological Sciences, Mount Sinai School of Medicine, New York, NY 10029, USA.

Genetics
|March 3, 2010
PubMed

Insights

Fission yeast Tra1 protein, a TRRAP homolog, regulates cell cycle timing. Mutations in Tra1 affect Wee1 protein levels, impacting mitotic entry even when Chk1 is overexpressed, revealing a new role in cell cycle control.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • The G2 DNA damage checkpoint prevents mitotic entry by inhibiting Cdc2 via Chk1 kinase.
  • Chk1 kinase regulates Wee1 and Cdc25 phosphatases for cell cycle arrest.
  • Overexpression of Chk1 can induce G2 arrest independently of DNA damage.

Purpose of the Study:

  • To identify fission yeast genes that confer resistance to Chk1 overexpression.
  • To elucidate the role of Tra1 in regulating the G2/M cell cycle transition.

Main Methods:

  • Fission yeast genetic screen for resistance to overexpressed chk1(+).
  • Analysis of tra1 mutations and their effect on cell cycle progression and protein levels.
  • Investigation of histone acetyltransferase (HAT) and deacetylase (HDAC) activity involvement.
  • Examination of the interaction between Tra1, Wee1, and Cdr kinases.

Main Results:

  • A mutation in tra1, encoding a TRRAP homolog, confers resistance to Chk1 overexpression.
  • Tra1 regulates Wee1 protein accumulation and function, impacting mitotic entry timing.
  • Tra1-dependent regulation of Wee1 requires Cdr1 and Cdr2 kinases.
  • Inhibition of histone deacetylases reverses the resistance phenotype, suggesting HAT activity.

Conclusions:

  • Tra1 is a novel component in the regulation of mitotic entry timing.
  • Tra1 influences Wee1 activity, a key regulator of Cdc2 activation.
  • Tra1's function in cell cycle control may involve its role in scaffolding HAT complexes.

More Related Videos

Mapping the Structure-Function Relationships of Disordered Oncogenic Transcription Factors Using Transcriptomic Analysis09:58

Mapping the Structure-Function Relationships of Disordered Oncogenic Transcription Factors Using Transcriptomic Analysis

Published on: June 27, 2020

Identifying Protein-protein Interaction in Drosophila Adult Heads by Tandem Affinity Purification (TAP)10:36

Identifying Protein-protein Interaction in Drosophila Adult Heads by Tandem Affinity Purification (TAP)

Published on: December 5, 2013

Related Concept Videos

Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
Master Transcription Regulators02:23

Master Transcription Regulators

Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
Master Transcription Regulators02:23

Master Transcription Regulators

Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
Cotranslational Protein Translocation01:20

Cotranslational Protein Translocation

Translocation of proteins across membranes is an ancient process that occurs even in bacteria and archaebacteria. In fact, the components of the translocation machinery are still conserved between prokaryotes and eukaryotes.
Sec61 channel partners for cotranslational translocation
During cotranslational translocation, the Sec61 channel partners with the signal recognition particle (SRP), the signal recognition particle receptor (SR), and the ribosomes to transport the nascent polypeptide chain...
The Unfolded Protein Response01:37

The Unfolded Protein Response

The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
Protein Translocation Machinery on the ER Membrane01:28

Protein Translocation Machinery on the ER Membrane

The translocon complex situated on the ER membrane is the main gateway for the protein secretory pathway. It facilitates the transport of nascent peptides into the ER lumen and their insertion into the ER membrane.
Sec61 protein conducting channel
In eukaryotes, the translocon complex comprises a core heterotrimeric translocator channel called the Sec61 complex. This channel includes three transmembrane proteins, Sec61α, Sec61β, and Sec61γ, and is the largest subunit of the translocon complex.