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Related Concept Videos

The DNA Replication Fork01:02

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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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Translesion DNA Polymerases02:10

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Translesion (TLS) polymerases rescue stalled DNA polymerases at sites of damaged bases by replacing the replicative polymerase and installing a nucleotide across the damaged site. Doing so, TLS allows additional time for the cell to repair the damage before resuming regular DNA replication.
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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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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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Direct Restart of a Replication Fork Stalled by a Head-On RNA Polymerase
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Conflicts with transcription make early replication late.

Eva Petermann1

  • 1Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham B15 2TT, UK; Birmingham Centre for Genome Biology, University of Birmingham, Birmingham B15 2TT, UK.

Molecular Cell
|September 16, 2022
PubMed
Summary

Conflicts between DNA replication and transcription in early S phase lead to under-replicated DNA persisting into mitosis, as shown by sequencing DNA synthesis sites in cells lacking homologous recombination.

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Area of Science:

  • Molecular Biology
  • Genetics
  • Cell Biology

Background:

  • Conflicts between DNA replication and transcription pose a threat to genome stability.
  • Understanding how these conflicts are resolved or lead to genomic instability is crucial.

Purpose of the Study:

  • To investigate the consequences of transcription-replication conflicts during early S phase.
  • To determine how cells lacking homologous recombination handle these conflicts.

Main Methods:

  • Sequencing of DNA synthesis sites.
  • Analysis of cells deficient in homologous recombination.

Main Results:

  • Identified specific sites of DNA synthesis during mitosis.
  • Demonstrated that transcription-replication conflicts in early S phase result in under-replicated DNA.
  • Showed that this under-replicated DNA persists into mitosis in the absence of homologous recombination.

Conclusions:

  • Homologous recombination plays a role in resolving conflicts that lead to under-replicated DNA.
  • Transcription-replication conflicts are a significant source of genomic instability, particularly in cells with compromised DNA repair pathways.