Related Experiment Video

Updated: May 16, 2026

Two- and Three-Dimensional Live Cell Imaging of DNA Damage Response Proteins
10:24

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

Published on: September 28, 2012

CtIP- and ATR-dependent FANCJ phosphorylation in response to DNA strand breaks mediated by DNA replication

Ryo Sakasai1, Akiko Sakai, Makoto Iimori

  • 1Innovative Anticancer Strategy for Therapeutics and Diagnosis Group, Innovation Center for Medical Redox Navigation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.

Genes to Cells : Devoted to Molecular & Cellular Mechanisms
|November 20, 2012
PubMed

Insights

DNA damage triggers FANCJ hyperphosphorylation, a process crucial for DNA repair. This modification, dependent on DNA end resection and ATR kinase, involves FANCJ-TopBP1 complex formation.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cancer Research

Background:

  • FANCJ (BACH1/BRIP1) is a DEAH helicase implicated in Fanconi anemia and cancer risk.
  • Its role in DNA double-strand break (DSB) repair and cell cycle checkpoints is known, but its regulation is unclear.

Purpose of the Study:

  • To investigate the DNA damage-induced phosphorylation of FANCJ.
  • To elucidate the molecular mechanisms regulating FANCJ activity in response to DNA damage.

Main Methods:

  • Induction of DNA double-strand breaks (DSBs) and replication fork stalling using chemical agents like camptothecin (CPT).
  • Analysis of FANCJ hyperphosphorylation, its dependence on ATR kinase and TopBP1, and the role of DNA end resection.
  • Assessment of FANCJ-TopBP1 complex formation under various conditions.

Main Results:

  • DSBs and replication fork stalling induce FANCJ hyperphosphorylation.
  • CPT treatment causes rapid FANCJ hyperphosphorylation dependent on TopBP1 and ATR kinase.
  • DNA end resection is required for FANCJ hyperphosphorylation.
  • CPT treatment increases the FANCJ-TopBP1 complex, independent of ATR-dependent hyperphosphorylation.

Conclusions:

  • FANCJ function is modulated by ATR-dependent hyperphosphorylation in response to DNA end resection.
  • FANCJ activity is also regulated by FANCJ-TopBP1 complex formation during replication-coupled DSBs.

More Related Videos

Capturing Common Fragile Site Breaks by Native γH2A.X ChIP09:46

Capturing Common Fragile Site Breaks by Native γH2A.X ChIP

Published on: January 24, 2025

Characterizing DNA Repair Processes at Transient and Long-lasting Double-strand DNA Breaks by Immunofluorescence Microscopy08:31

Characterizing DNA Repair Processes at Transient and Long-lasting Double-strand DNA Breaks by Immunofluorescence Microscopy

Published on: June 8, 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...
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...
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...
Fixing Double-strand Breaks02:04

Fixing Double-strand Breaks

The double-stranded structure of DNA has two major advantages. First, it serves as a safe repository of genetic information where one strand serves as the back-up in case the other strand is damaged. Second, the double-helical structure can be wrapped around proteins called histones to form nucleosomes, which can then be tightly wound to form chromosomes. This way, DNA chains up to 2 inches long can be contained within microscopic structures in a cell. A double-stranded break not only damages...
Fixing Double-strand Breaks02:04

Fixing Double-strand Breaks

The double-stranded structure of DNA has two major advantages. First, it serves as a safe repository of genetic information where one strand serves as the back-up in case the other strand is damaged. Second, the double-helical structure can be wrapped around proteins called histones to form nucleosomes, which can then be tightly wound to form chromosomes. This way, DNA chains up to 2 inches long can be contained within microscopic structures in a cell. A double-stranded break not only damages...