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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, a...
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...
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 forks, one in...
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 forks, one in...
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...
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...

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Quantifying Replication Stress in Ovarian Cancer Cells Using Single-Stranded DNA Immunofluorescence
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Quantifying Replication Stress in Ovarian Cancer Cells Using Single-Stranded DNA Immunofluorescence

Published on: February 10, 2023

Break-induced replication and genome stability.

Cynthia J Sakofsky1, Sandeep Ayyar, Anna Malkova

  • 1Department of Biology, School of Science, IUPUI, Indianapolis, Indiana 46202, USA.

Biomolecules
|June 15, 2013
PubMed
Summary
This summary is machine-generated.

Break-induced replication (BIR) repairs DNA double-strand breaks (DSBs) but can cause genomic instability and mutations. This pathway, including micro-homology-mediated BIR (MMBIR), contributes to diseases and evolution.

Keywords:
DNA repairbreak-induced replication (BIR)double-strand break (DSB)recombination

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Detection of DNA Breaks in Dividing Human Cells by Neutral Comet Assay
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Quantifying Replication Stress in Ovarian Cancer Cells Using Single-Stranded DNA Immunofluorescence
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Detection of DNA Breaks in Dividing Human Cells by Neutral Comet Assay
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Detection of DNA Breaks in Dividing Human Cells by Neutral Comet Assay

Published on: August 23, 2024

Area of Science:

  • Genetics
  • Molecular Biology
  • Genomics

Background:

  • Genetic instabilities, including mutations and chromosomal rearrangements, are implicated in cancer, disease, and evolution.
  • Double-strand DNA breaks (DSBs) are a significant cause of genetic instability.
  • DSBs can arise from various endogenous and exogenous cellular factors.

Purpose of the Study:

  • To explore the role of break-induced replication (BIR) in repairing DSBs.
  • To investigate how BIR contributes to genomic instability and associated diseases.
  • To understand the mutagenic potential and consequences of BIR and related pathways.

Main Methods:

  • The study focuses on the mechanism of break-induced replication (BIR) for repairing DSBs with a single rejoining end.
  • It examines the consequences of BIR, including loss of heterozygosity, telomere maintenance, and translocations.
  • The research also considers micro-homology-mediated BIR (MMBIR) and its role in copy-number variations and complex rearrangements.

Main Results:

  • BIR is a critical repair pathway for DSBs lacking one end, often occurring due to telomere erosion or replication fork collapse.
  • BIR can lead to significant genetic instability, including high mutation rates (approximately 1000-fold higher than normal replication).
  • MMBIR, a related mechanism, generates copy-number variations and complex chromosomal rearrangements.

Conclusions:

  • Activation of BIR can be a dangerous source of genomic destabilization.
  • BIR and MMBIR contribute to various genetic instabilities with substantial biological and health consequences.
  • Understanding BIR is crucial for comprehending cancer development and human health.