Related Experiment Video

Updated: Aug 26, 2025

Visualization of DNA Repair Proteins Interaction by Immunofluorescence
07:55

Visualization of DNA Repair Proteins Interaction by Immunofluorescence

Published on: June 26, 2020

10.3K

S6K1 phosphorylates Cdk1 and MSH6 to regulate DNA repair

Adi Amar-Schwartz1, Vered Ben Hur1, Amina Jbara1

  • 1Department of Biochemistry and Molecular Biology, the Institute for Medical Research Israel-Canada, Hebrew University-Hadassah Medical School, Jerusalem, Israel.

Elife
|October 3, 2022
PubMed

Insights

The study reveals that S6 Kinase 1 (S6K1) plays a crucial role in DNA repair by regulating cell cycle progression and enhancing homologous recombination and mismatch repair mechanisms. This discovery highlights S6K1

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Cancer Research

Background:

  • The mTORC1 signaling pathway is implicated in DNA damage response, but its direct role in DNA repair remains unclear.
  • S6 Kinase 1 (S6K1), a key substrate of mTORC1, is known for regulating cell growth and metabolism.

Purpose of the Study:

  • To investigate the direct role and mechanism of the mTORC1-S6K1 signaling pathway in DNA repair.
  • To elucidate how S6K1 regulates homologous recombination (HR) and mismatch repair (MMR) pathways.

Main Methods:

  • Investigated S6K1's role in DNA repair mechanisms.
  • Analyzed the phosphorylation of Cdk1 and MSH6 by S6K1.
  • Examined breast cancer cell lines with RPS6KB1 gene amplification.
  • Correlated S6K1 expression with patient survival data.

Main Results:

  • S6K1 orchestrates DNA repair by phosphorylating Cdk1 (at serine 39), inducing G2/M cell cycle arrest for homologous recombination.
  • S6K1 enhances mismatch repair by phosphorylating MSH6 (at serine 309).
  • Breast cancer cells with RPS6KB1 amplification exhibit resistance to DNA damaging agents, and high S6K1 expression correlates with poor chemotherapy outcomes.

Conclusions:

  • S6K1 has a novel function in regulating DNA repair through cell cycle control, HRR, and MMR.
  • S6K1 acts as a tumorigenic factor by maintaining genomic stability, potentially through DNA repair.
  • Targeting S6K1 may offer therapeutic strategies for overcoming chemotherapy resistance in breast cancer.
Keywords:
CDK1DNA repairMSH2MSH6S6K1biochemistrycancer biologycdk1(cdc2)chemical biologydna repairmTORC1msh2msh6s6k1

More Related Videos

Application of Stopped-flow Kinetics Methods to Investigate the Mechanism of Action of a DNA Repair Protein11:01

Application of Stopped-flow Kinetics Methods to Investigate the Mechanism of Action of a DNA Repair Protein

Published on: March 31, 2010

18.2K
Visualizing and Quantifying Endonuclease-Based Site-Specific DNA Damage10:59

Visualizing and Quantifying Endonuclease-Based Site-Specific DNA Damage

Published on: August 21, 2021

3.7K

Related Concept Videos

DNA Damage can Stall the Cell Cycle02:37

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
9.3K
S-Cdk Initiates DNA Replication02:38

S-Cdk Initiates DNA Replication

The cell cycle is a series of events leading to DNA duplication followed by the division of cell content to form two daughter cells. The cell cycle progresses in four stages—the cell increases in size (gap 1 or G1-phase), duplicates its DNA (synthesis or S-phase), prepares to divide (gap 2 or G2-phase), and divides (mitosis or M-phase).
Two states at the origin of replication
In eukaryotes, the initiation of replication occurs at many sites on the chromosomes, called the origins of...
4.8K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.9K
M-Cdk Drives Transition Into Mitosis02:15

M-Cdk Drives Transition Into Mitosis

Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
5.7K
Mismatch Repair01:20

Mismatch Repair

Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
5.1K
Positive Regulator Molecules02:39

Positive Regulator Molecules

Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
5.6K