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Related Concept Videos

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In eukaryotic cells, DNA replication is highly conserved and tightly regulated. Multiple linear chromosomes must be duplicated with high fidelity before cell division, so there are many proteins that fulfill specialized roles in the replication process. Replication occurs in three phases: initiation, elongation, and termination, and ends with two complete sets of chromosomes in the nucleus.
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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...
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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,...
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Inducing a Site Specific Replication Blockage in E. coli Using a Fluorescent Repressor Operator System
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Break induced replication in eukaryotes: mechanisms, functions, and consequences.

Cynthia J Sakofsky1, Anna Malkova2

  • 1a Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences , US National Institutes of Health , Research Triangle Park , NC , USA.

Critical Reviews in Biochemistry and Molecular Biology
|April 22, 2017
PubMed
Summary
This summary is machine-generated.

Break-induced replication (BIR) repairs one-ended DNA breaks using a unique synthesis mechanism. This process, though vital for repair, can cause significant genetic instability and rearrangements in DNA.

Keywords:
Break-induced replicationRad51-dependent break-induced replicationRad51-independent break-induced replicationalternative lengthening of telomereshalf-crossovermicrohomology-mediated break-induced replicationmutation cluster

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Area of Science:

  • Molecular Biology
  • Genetics
  • Genomics

Background:

  • Break-induced replication (BIR) is a critical DNA repair pathway.
  • It specializes in repairing one-ended double-strand DNA breaks (DSBs), often arising from collapsed replication forks or telomere erosion.

Purpose of the Study:

  • To elucidate the mechanisms and consequences of BIR.
  • To highlight its role in both DNA repair and genomic instability.

Main Methods:

  • Utilized experimental systems in budding yeast and other organisms, including humans.
  • Investigated BIR initiated in various cellular contexts, such as collapsed replication forks and telomere maintenance.
  • Advanced understanding of microhomology-mediated BIR (MMBIR).

Main Results:

  • BIR involves DNA synthesis over long distances, distinct from standard replication, proceeding via a migrating bubble.
  • This process is linked to significant genetic instabilities: hyper-mutagenesis, loss of heterozygosity, translocations, copy-number variations, and complex genomic rearrangements.
  • MMBIR was shown to promote complex chromosomal rearrangements relevant to cancer and neurological disorders.

Conclusions:

  • BIR is a powerful DNA repair mechanism with a dual role in maintaining genome integrity and driving genetic instability.
  • Understanding BIR and MMBIR is crucial for comprehending diseases associated with genomic rearrangements.