Related Experiment Video

Updated: Sep 5, 2025

Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors
06:07

Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors

Published on: August 5, 2022

2.7K

SMYD3 Impedes Small Cell Lung Cancer Sensitivity to Alkylation Damage through RNF113A Methylation-Phosphorylation

Valentina Lukinović1, Simone Hausmann2, Gael S Roth1,3

  • 1Institute for Advanced Biosciences, Grenoble Alpes University, CNRS UMR5309, INSERM U1209, Grenoble, France.

Cancer Discovery
|July 12, 2022
PubMed

Insights

Small cell lung cancer (SCLC) rapidly develops chemoresistance. Targeting SMYD3, a key regulator of DNA damage response, restores sensitivity to chemotherapy, offering new treatment strategies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Small cell lung cancer (SCLC) presents a critical challenge due to poor survival rates, limited treatments, and swift chemoresistance.
  • The alkylation damage response pathway is crucial for SCLC survival and treatment resistance.

Purpose of the Study:

  • To identify key regulators of SCLC chemoresistance.
  • To investigate the role of SMYD3 in SCLC sensitivity to alkylation-based chemotherapy.

Main Methods:

  • Investigated the role of lysine methyltransferase SMYD3 in SCLC.
  • Analyzed the interaction between SMYD3, RNF113A, and PP4.
  • Assessed the effect of SMYD3 inhibition on SCLC response to chemotherapy.

Main Results:

  • SMYD3 upregulates RNF113A methylation, impairing its interaction with PP4 and controlling phosphorylation.
  • This posttranslational modification cross-talk maintains RNF113A E3 ligase activity, vital for alkylation damage response.
  • SMYD3 inhibition restores SCLC sensitivity to alkylating agents, enhancing chemotherapy response.

Conclusions:

  • SMYD3 is a critical mediator of SCLC sensitivity to alkylation chemotherapy.
  • Inhibiting SMYD3 offers a promising strategy to overcome chemoresistance in SCLC.
  • Targeting SMYD3 can improve patient outcomes by resensitizing SCLC to established chemotherapies.

More Related Videos

CD Spectroscopy to Study DNA-Protein Interactions06:48

CD Spectroscopy to Study DNA-Protein Interactions

Published on: February 10, 2022

6.9K
Author Spotlight: Developing Novel Anticancer Therapeutics Targeting the DNA Damage Response05:01

Author Spotlight: Developing Novel Anticancer Therapeutics Targeting the DNA Damage Response

Published on: June 14, 2024

1.5K

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
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.6K
Nucleosome Remodeling02:54

Nucleosome Remodeling

Nucleosomes are the basic units of chromatin compaction. Each nucleosome consists of the DNA bound tightly around a histone core, which makes the DNA inaccessible to DNA binding proteins such as DNA polymerase and RNA polymerase. Hence, the fundamental problem is to ensure access to DNA when appropriate, despite the compact and protective chromatin structure.
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
9.4K
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...
5.2K
Epigenetic Regulation01:46

Epigenetic Regulation

Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
31.3K
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
35.8K