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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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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...
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Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
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Related Experiment Video

Updated: Jun 24, 2025

Detection of Homologous Recombination Intermediates via Proximity Ligation and Quantitative PCR in Saccharomyces cerevisiae
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MCM8 interacts with DDX5 to promote R-loop resolution.

Canxin Wen1,2,3,4,5,6,7, Lili Cao1,2,3,4,5,6,7, Shuhan Wang1,2,3,4,5,6,7

  • 1State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University, Jinan, Shandong, 250012, China.

The EMBO Journal
|June 10, 2024
PubMed
Summary

MCM8 protein is vital for germ cell development and fertility. Loss of MCM8 causes R-loop accumulation, leading to genome instability and impaired reproductive aging in mice.

Keywords:
FertilityGenome StabilityMCM8Primordial Germ CellsR-loop

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Area of Science:

  • Genetics
  • Reproductive Biology
  • Genomic Stability

Background:

  • MCM8 is a key gene in reproductive aging and meiotic repair.
  • Its role in mitotic germ cells and genome stability was previously unclear.

Purpose of the Study:

  • To investigate the function of MCM8 in mitotic germ cells.
  • To understand MCM8's role in maintaining genome integrity and reproductive health.

Main Methods:

  • Disabling MCM8 gene in mice.
  • Analyzing primordial germ cell (PGC) proliferation and fertility.
  • Investigating MCM8's interaction with helicases DDX5 and DHX9.
  • Assessing R-loop accumulation and DNA damage.

Main Results:

  • MCM8 deficiency caused PGC proliferation defects and infertility in mice.
  • MCM8 loss led to R-loop accumulation by reducing DDX5 and DHX9 helicase retention.
  • Mutant MCM8 with reduced DDX5 interaction showed increased R-loop levels.
  • This induced genome instability in germ cells.

Conclusions:

  • MCM8 interacts with R-loop resolving factors to prevent DNA damage.
  • MCM8 is essential for PGC development and maintaining genome integrity.
  • This study enhances understanding of MCM8's role in reproductive aging and germ cell genome stability.