Related Experiment Video

Updated: Jun 23, 2026

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

Solving the RIDDLE of 53BP1 recruitment to sites of damage

Grant S Stewart1

  • 1Cancer Research UK Institute for Cancer Studies, University of Birmingham, Edgbaston, Birmingham, UK. g.s.stewart@bham.ac.uk

Cell Cycle (Georgetown, Tex.)
|April 18, 2009
PubMed

Insights

The E3 ubiquitin ligase RNF168 is crucial for DNA double-strand break (DSB) repair and immune development. Mutations in RNF168 cause RIDDLE syndrome, linking ubiquitylation to DNA repair and immunity.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cellular Biology

Background:

  • DNA double-strand breaks (DSBs) trigger complex cellular responses essential for genome integrity.
  • The PI-3-kinase-like kinase family (ATM, ATR, DNA-PK) coordinates these responses.
  • Mutations in DSB repair genes lead to genomic instability and various diseases.

Purpose of the Study:

  • To investigate the role of E3 ubiquitin ligases in DNA double-strand break (DSB) repair.
  • To understand the genetic basis of RIDDLE syndrome and its connection to DNA repair and immunity.
  • To elucidate the ubiquitylation cascade in DSB repair protein recruitment.

Main Methods:

  • Studying cells from patients with inherited mutations in DSB repair genes.
  • Identifying mutations in E3 ubiquitin ligase RNF168 as the cause of RIDDLE syndrome.
  • Analyzing the function of RNF168 in relation to RNF8 in DSB repair pathways.

Main Results:

  • The E3 ubiquitin ligase RNF8 is a key regulator of DNA DSB repair.
  • RNF168 acts downstream of RNF8 to recruit repair proteins like BRCA1 and 53BP1 to DNA damage sites.
  • Mutations in RNF168 cause RIDDLE syndrome, a DNA repair deficiency disorder.

Conclusions:

  • RNF8 and RNF168 form a ubiquitylation cascade critical for orchestrating DSB repair protein localization.
  • RNF168 is the first identified link between ubiquitin-dependent DSB repair and human immune system development.
  • Understanding this pathway is vital for diseases associated with genomic instability and immune dysfunction.

More Related Videos

Two- and Three-Dimensional Live Cell Imaging of DNA Damage Response Proteins10:24

Two- and Three-Dimensional Live Cell Imaging of DNA Damage Response Proteins

Published on: September 28, 2012

Investigation of Protein Recruitment to DNA Lesions Using 405 Nm Laser Micro-irradiation12:29

Investigation of Protein Recruitment to DNA Lesions Using 405 Nm Laser Micro-irradiation

Published on: March 20, 2018

Related Concept Videos

DNA Damage can Stall the Cell Cycle02:36

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...
DNA Damage Can Stall the Cell Cycle02:36

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...
Homologous Recombination02:31

Homologous Recombination

The basic reaction of homologous recombination (HR) involves two chromatids that contain DNA sequences sharing a significant stretch of identity. One of these sequences uses a strand from another as a template to synthesize DNA in an enzyme-catalyzed reaction. The final product is a novel amalgamation of the two substrates. To ensure an accurate recombination of sequences, HR is restricted to the S and G2 phases of the cell cycle. At these stages, the DNA has been replicated already and the...
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, a...
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:
Translesion DNA Polymerases02:10

Translesion DNA Polymerases

Translesion (TLS) polymerases rescue stalled DNA polymerases at sites of damaged bases by replacing the replicative polymerase and installing a nucleotide across the damaged site. Doing so, TLS allows additional time for the cell to repair the damage before resuming regular DNA replication.
TLS polymerases are found in all three domains of life - archaea, bacteria, and eukaryotes. Of the different classes of TLS polymerases, members of the Y family are fitted with specialized structures that...