Related Experiment Video

Updated: Apr 24, 2026

Capturing Common Fragile Site Breaks by Native γH2A.X ChIP
09:46

Capturing Common Fragile Site Breaks by Native γH2A.X ChIP

Published on: January 24, 2025

706

Replication fork recovery and regulation of common fragile sites stability

Annapaola Franchitto1, Pietro Pichierri

  • 1Section of Molecular Epidemiology, Department of Environment and Primary Prevention, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161, Rome, Italy, annapaola.franchitto@iss.it.

Cellular and Molecular Life Sciences : CMLS
|September 14, 2014
PubMed

Insights

Genomic instability, a cancer trigger, involves common fragile sites (CFS). DNA replication stress impairs CFS integrity, highlighting the need for proteins that stabilize stalled replication forks to prevent cancer development.

Area of Science:

  • Genetics
  • Molecular Biology
  • Cancer Research

Background:

  • Genomic instability is a key factor in cancer development.
  • Common fragile sites (CFS) are vulnerable regions in the human genome prone to chromosomal instability during replicative stress.
  • The precise mechanisms underlying CFS expression and the cellular factors preventing CFS instability are not fully understood.

Purpose of the Study:

  • To investigate the mechanisms leading to common fragile site (CFS) instability.
  • To identify cellular factors crucial for maintaining CFS integrity under replicative stress.
  • To elucidate the role of replication fork dynamics in CFS stability.

Main Methods:

  • Analysis of DNA replication stress responses.
  • Investigation of protein functions related to replication fork recovery and recombination.
  • Assessment of CFS expression under varying cellular conditions.

Main Results:

  • DNA is more susceptible to breakage when DNA replication is impaired.
  • Replication fork progression is perturbed at fragile sites due to intrinsic features and replication events.
  • Downregulation or mutation of proteins involved in stalled fork recovery or recombination increases CFS expression.

Conclusions:

  • Stabilization and recovery of perturbed replication forks are essential for maintaining CFS integrity.
  • Cellular mechanisms that ensure safe replication fork progression are critical for preventing genomic instability and cancer development.

More Related Videos

Detection of Post-Replicative Gaps Accumulation and Repair in Human Cells Using the DNA Fiber Assay10:32

Detection of Post-Replicative Gaps Accumulation and Repair in Human Cells Using the DNA Fiber Assay

Published on: February 3, 2022

6.7K
Inducing a Site Specific Replication Blockage in E. coli Using a Fluorescent Repressor Operator System11:19

Inducing a Site Specific Replication Blockage in E. coli Using a Fluorescent Repressor Operator System

Published on: August 21, 2016

8.5K

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,...
5.0K
Restarting Stalled Replication Forks02:37

Restarting Stalled Replication Forks

1.4K
The DNA Replication Fork01:02

The DNA Replication Fork

An organism’s genome needs to be duplicated in an efficient and error-free manner for its growth and survival. The replication fork is a Y-shaped active region where two strands of DNA are separated and replicated continuously. The coupling of DNA unzipping and complementary strand synthesis is a characteristic feature of a replication fork.   Organisms with small circular DNA, such as E. coli, often have a single origin of replication; therefore, they have only two replication...
30.4K
The DNA Replication Fork01:02

The DNA Replication Fork

17.5K
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...
58.6K
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...
8.5K