Related Experiment Video

Updated: Jun 14, 2025

Laser Microirradiation to Study In Vivo Cellular Responses to Simple and Complex DNA Damage
10:44

Laser Microirradiation to Study In Vivo Cellular Responses to Simple and Complex DNA Damage

Published on: January 31, 2018

10.2K

PARP1-TRIM44-MRN loop dictates the response to PARP inhibitors

Yonghyeon Kim1, Sunwoo Min1,2, Soyeon Kim3

  • 1Department of Biochemistry, Ajou University School of Medicine, Suwon 16499, Republic of Korea.

Nucleic Acids Research
|September 1, 2024
PubMed

Insights

Researchers identified TRIM44 as a key mediator in DNA repair. This protein links PARP1 to the ATM pathway, influencing homologous recombination repair (HRR) and potentially enhancing PARP inhibitor effectiveness.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cancer Research

Background:

  • Poly (ADP-ribose) polymerase inhibitors (PARPi) demonstrate efficacy in tumors with homologous recombination repair (HRR) defects.
  • The precise mechanism activating the HRR pathway in PARPi-treated cells remains unclear.

Purpose of the Study:

  • To identify the mediator connecting PARP1 and ATM pathways in DNA repair.
  • To elucidate the role of TRIM44 in homologous recombination repair and PARPi response.

Main Methods:

  • Screening of 211 human ubiquitin-related proteins to identify key mediators.
  • Investigating the interaction of TRIM44 with PARP1 and the MRN complex.
  • Assessing the impact of TRIM44 knockdown on cellular sensitivity to olaparib.

Main Results:

  • TRIM44 was identified as a crucial mediator that recruits the MRN complex to damaged chromatin, independent of PARP1 activity.
  • TRIM44 regulates the ubiquitination-PARylation balance of PARP1, facilitating MRN complex recruitment for double-strand break (DSB) repair.
  • TRIM44 knockdown increased sensitivity to olaparib and overcame resistance associated with 53BP1 deficiency.

Conclusions:

  • TRIM44 plays a central role in linking PARP1 to the ATM-mediated DNA repair pathway.
  • Targeting TRIM44 could enhance PARPi efficacy and potentially expand their application to HR-proficient tumors.

More Related Videos

Cell Death Associated with Abnormal Mitosis Observed by Confocal Imaging in Live Cancer Cells15:53

Cell Death Associated with Abnormal Mitosis Observed by Confocal Imaging in Live Cancer Cells

Published on: August 21, 2013

14.9K
Assessment of Global DNA Double-Strand End Resection using BrdU-DNA Labeling coupled with Cell Cycle Discrimination Imaging06:44

Assessment of Global DNA Double-Strand End Resection using BrdU-DNA Labeling coupled with Cell Cycle Discrimination Imaging

Published on: April 28, 2021

3.9K

Related Concept Videos

Restarting Stalled Replication Forks02:37

Restarting Stalled Replication Forks

DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart,...
5.8K
Long-patch Base Excision Repair01:02

Long-patch Base Excision Repair

Since the discovery of the two BER pathways, there has been a debate about how a cell chooses one pathway over the other and the factors determining this selection. Numerous in vitro experiments have pointed out multiple determinants for the sub-pathway selection. These are:
7.0K
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...
9.1K
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...
4.8K
Base Excision Repair01:54

Base Excision Repair

One of the common DNA damages is the chemical alteration of single bases by alkylation, oxidation, or deamination. The altered bases cause mispairing and strand breakage during replication. This type of damage causes minimal change to the DNA double helix structure and can be repaired by the base excision repair (BER) pathways. BER corrects damaged DNA sequences by removing the damaged base and restoring the original base sequence using the complementary strand as a template.
The first step of...
22.2K
Nucleotide Excision Repair01:38

Nucleotide Excision Repair

DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
3.5K