Related Experiment Video

Updated: Jan 21, 2026

Using the Threat Probability Task to Assess Anxiety and Fear During Uncertain and Certain Threat
11:18

Using the Threat Probability Task to Assess Anxiety and Fear During Uncertain and Certain Threat

Published on: September 12, 2014

15.7K

Mck1 defines a key S-phase checkpoint effector in response to various degrees of replication threats

Xiaoli Li1, Xuejiao Jin2,3, Sushma Sharma4

  • 1State Key Laboratory of Agro-Biotechnology and Beijing Advanced Innovation Center for Food Nutrition and Human Health, MOA Key Laboratory of Soil Microbiology, College of Biological Sciences, China Agricultural University, Beijing, P.R. China.

Plos Genetics
|August 6, 2019
PubMed

Insights

The S-phase checkpoint uses Mck1 and Dun1 kinases to regulate DNA replication. Mck1 releases the Crt1 repressor, controlling ribonucleotide reductase (RNR) activity and dNTP levels during replication stress.

Area of Science:

  • Cellular biology
  • Molecular genetics
  • DNA replication and repair

Background:

  • The S-phase checkpoint is crucial for maintaining genomic stability by regulating DNA replication.
  • Eukaryotic cells must adapt to varying levels of replication stress to preserve dNTP pools.
  • The precise mechanisms by which cells manage replication threats remain incompletely understood.

Purpose of the Study:

  • To elucidate the roles of the conserved GSK-3 kinase Mck1 and Dun1 in the S-phase checkpoint.
  • To investigate how Mck1 and Dun1 cooperate to regulate ribonucleotide reductase (RNR) activity and dNTP homeostasis.
  • To understand the cellular response to different levels of replication stress.

Main Methods:

  • Genetic analysis involving deletion mutants (mck1Δ, dun1Δ, mec1Δ, rad53Δ, hug1Δ, crt1Δ).
  • Hydroxyurea (HU) treatment to induce replication stress.
  • Analysis of DNA damage-inducible gene expression (RNR2-4, HUG1).
  • Assessment of Crt1 repressor release from gene promoters.
  • Measurement of dNTP levels and cell survival rates.

Main Results:

  • Mck1 acts downstream of Rad53 and cooperates with Dun1 in the S-phase checkpoint.
  • Mck1 phosphorylates and releases the Crt1 repressor from RNR and HUG1 promoters.
  • Hug1, an Rnr2 inhibitor, is induced by Mck1 to counterbalance excessive RNR activity.
  • Under severe stress, Mck1 inhibits HUG1 transcription.
  • Combined deletion of HUG1 and CRT1 dramatically increases dNTP levels and enhances survival in mck1Δdun1Δ or mec1Δ cells under lethal HU treatment.

Conclusions:

  • Mck1 and Dun1 exhibit a division of labor within the S-phase checkpoint pathway.
  • This cooperation allows for fine-tuning of dNTP homeostasis in response to replication stress.
  • The Mck1-Crt1-Hug1 axis provides a critical regulatory mechanism for managing dNTP pools during DNA replication.

More Related Videos

Continuous Theta Burst Stimulation of the Posterior Medial Frontal Cortex to Experimentally Reduce Ideological Threat Responses06:42

Continuous Theta Burst Stimulation of the Posterior Medial Frontal Cortex to Experimentally Reduce Ideological Threat Responses

Published on: September 28, 2018

12.1K
Study of the DNA Damage Checkpoint using Xenopus Egg Extracts10:55

Study of the DNA Damage Checkpoint using Xenopus Egg Extracts

Published on: November 5, 2012

17.1K

Related Concept Videos

Chromosome Replication02:31

Chromosome Replication

Before a cell can divide, it must accurately replicate all of its chromosomes, including the DNA and its associated histone and non-histone proteins.  This process begins at numerous origins of replication during the S phase of the cell cycle in each of a cell’s chromosomes simultaneously. Certain nucleotides can act as origins of replication, but these sequences are not well defined - especially in complex, multi-cellular, eukaryotic species. The length of DNA that spans an origin...
10.5K
Stereotype Threat and Self-fulfilling Prophecies02:09

Stereotype Threat and Self-fulfilling Prophecies

When we hold a stereotype about a person, we have expectations that he or she will fulfill that stereotype. A self-fulfilling prophecy is an expectation held by a person that alters his or her behavior in a way that tends to make it true. When we hold stereotypes about a person, we tend to treat the person according to our expectations. This treatment can influence the person to act according to our stereotypic expectations, thus confirming our stereotypic beliefs. Research by Rosenthal and...
41.9K
Threats to Biodiversity01:50

Threats to Biodiversity

There have been five major extinction events throughout geological history, resulting in the elimination of biodiversity, followed by a rebound of species that adapted to the new conditions. In the current geological epoch, the Holocene, there is a sixth extinction event in progress. This mass extinction has been attributed to human activities and is thus provisionally called the Anthropocene. In 2019 the human population reached 7.7 billion people and is projected to comprise 10 billion by...
26.6K
The Spindle Assembly Checkpoint02:19

The Spindle Assembly Checkpoint

The spindle assembly checkpoint is a molecular surveillance mechanism ensuring the fidelity of chromosome segregation during anaphase. The checkpoint monitors the completion of all the prerequisite steps before chromosome segregation to determine whether the segregation process should proceed or be delayed.
Many proteins function together to control the spindle assembly checkpoint. Mutations affecting these proteins may allow cells to proceed into anaphase prematurely, resulting in the...
3.7K
One-Degree-of-Freedom System01:24

One-Degree-of-Freedom System

In mechanical engineering, one-degree-of-freedom systems form the basis of a wide range of electrical and mechanical components. Using these models, engineers can predict the behavior of various parts in a larger system, which gives them insight into how different forces interact with each other.
A one-degree-of-freedom system is defined by an independent variable that determines its state and behavior. One example of a one-degree-of-freedom system is a simple harmonic oscillator, such as a...
817
Degrees of Freedom01:02

Degrees of Freedom

The degree of freedom for a particular statistical calculation is the number of values that are free to vary. Thus, the minimum number of independent numbers can specify a particular statistic. The degrees of freedom differ greatly depending on known and uncalculated statistical components.
For example, suppose there are three unknown numbers whose mean is 10; although we can freely assign values to the first and second numbers, the value of the last number can not be arbitrarily assigned.
6.8K