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Related Concept Videos

S-Cdk Initiates DNA Replication02:38

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The cell cycle is a series of events leading to DNA duplication followed by the division of cell content to form two daughter cells. The cell cycle progresses in four stages—the cell increases in size (gap 1 or G1-phase), duplicates its DNA (synthesis or S-phase), prepares to divide (gap 2 or G2-phase), and divides (mitosis or M-phase).
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Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome.  Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form...
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The organization of prokaryotic genes in their genome is notably different from that of eukaryotes. Prokaryotic genes are organized, such that the genes for proteins involved in the same biochemical process or function are located together in groups. This group of genes, along with their regulatory elements, are collectively known as an operon. The functional genes in an operon are transcribed together to give a single strand of mRNA known as polycistronic mRNA.
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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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Related Experiment Video

Updated: Jan 15, 2026

Visualization of DNA Replication in the Vertebrate Model System DT40 using the DNA Fiber Technique
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KCTD10 is a sensor for co-directional transcription-replication conflicts.

Jake A Kloeber1,2, Bin Chen1,3, Guangchao Sun4

  • 1Division of Oncology Research, Department of Oncology, Mayo Clinic, Rochester, MN, USA.

Nature
|October 8, 2025
PubMed
Summary

The CUL3-KCTD10 complex resolves transcription-replication conflicts (TRCs) by remodeling RNA polymerase, allowing DNA replication to proceed. This mechanism prevents genome instability and DNA damage.

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Related Experiment Videos

Last Updated: Jan 15, 2026

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Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • Transcription-replication conflicts (TRCs) are a significant source of genome instability in mammals.
  • The mechanisms by which cells manage TRCs and facilitate replisome bypass remain largely unknown.

Purpose of the Study:

  • To elucidate the molecular mechanisms by which cells resolve TRCs and maintain genome stability.
  • To identify the role of the CUL3-KCTD10 E3 ligase in managing conflicts between DNA replication and transcription.

Main Methods:

  • Investigated the interaction of KCTD10 with both the replisome and transcription machinery.
  • Analyzed the role of CUL3-KCTD10 in ubiquitination and removal of the RNA polymerase factor TCEA2.
  • Assessed the impact of KCTD10 deficiency on TRC accumulation and DNA damage.

Main Results:

  • CUL3-KCTD10 E3 ligase detects TRCs and promotes RNA polymerase remodeling for replisome bypass.
  • KCTD10 acts as a bivalent adaptor, sensing co-directional TRCs and facilitating CUL3 recruitment.
  • Absence of KCTD10 leads to increased TCEA2 retention, TRC accumulation, and DNA damage.

Conclusions:

  • The CUL3-KCTD10 complex bridges transcription and replication machinery to resolve conflicts.
  • This process is crucial for allowing DNA replication through transcriptionally active regions.
  • Findings provide a framework for understanding how transcription-replication coordination maintains genome stability.