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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...
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...
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...
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...

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Related Experiment Video

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Direct Restart of a Replication Fork Stalled by a Head-On RNA Polymerase
07:27

Direct Restart of a Replication Fork Stalled by a Head-On RNA Polymerase

Published on: April 29, 2010

Break-induced DNA replication.

Ranjith P Anand1, Susan T Lovett, James E Haber

  • 1Rosenstiel Basic Medical Sciences Research Center and Department of Biology, Brandeis University, Waltham, Massachusetts 02254-9110.

Cold Spring Harbor Perspectives in Biology
|July 25, 2013
PubMed
Summary
This summary is machine-generated.

Break-induced replication (BIR) repairs double-strand DNA breaks in eukaryotes, restarting stalled forks and protecting telomeres. However, BIR can also cause genome instability, leading to rearrangements and loss of heterozygosity.

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Area of Science:

  • Molecular Biology
  • Genetics
  • Genomics

Background:

  • Recombination-dependent DNA replication, known as break-induced replication (BIR), was first described in bacteriophage.
  • BIR is now recognized as a crucial mechanism for repairing double-strand chromosome breaks in eukaryotic cells.
  • This process is vital for restarting stalled replication forks and maintaining telomere integrity.

Purpose of the Study:

  • To elucidate the dual role of BIR in maintaining genome stability and promoting instability.
  • To understand the significance of BIR in eukaryotic DNA repair pathways.

Main Methods:

  • The study reviews existing literature on BIR mechanisms and outcomes.
  • Analysis of experimental data on DNA repair and replication fork restart.

Main Results:

  • BIR is essential for eukaryotic genome integrity, particularly in restarting stalled replication forks and preserving telomeres.
  • Despite its protective role, BIR can paradoxically drive genome instability.
  • BIR contributes to loss of heterozygosity, nonreciprocal translocations, and complex chromosomal rearrangements.

Conclusions:

  • BIR is a fundamental DNA repair mechanism in eukaryotes with a complex role.
  • While BIR safeguards the genome during replication stress, it also presents a significant source of genomic instability.
  • Further research is needed to fully understand and potentially modulate BIR's impact on genome stability.