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Related Concept Videos

Homologous Recombination02:31

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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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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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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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DNA Distortion and Damage
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Detection of Homologous Recombination Intermediates via Proximity Ligation and Quantitative PCR in Saccharomyces cerevisiae
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MePCE promotes homologous recombination through coordinating R-loop resolution at DNA double-stranded breaks.

Sravan K Devanathan1, Yi-Ru Li2, Samantha B Shelton1

  • 1Department of Molecular Biosciences, University of Texas at Austin, 2500 Speedway, Austin, TX 78712, USA.

Cell Reports
|May 24, 2025
PubMed
Summary
This summary is machine-generated.

MePCE protein regulates DNA repair by interacting with DNA double-stranded break (DSB) factors. Its depletion impairs homologous recombination repair and affects R-loop processing, explaining synthetic lethality with BRCA1 deficiency.

Keywords:
7SKBRCA1CP: Molecular biologyDNA repairDRIP-MSDRIP-seqFACTLARP7MePCER-loopshomologous recombination

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Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • MePCE protein regulates transcription elongation factor P-TEFb partitioning.
  • Its role in chromatin function, particularly DNA repair, is not well understood.
  • The 7SK ribonuclear protein complex (RNPc) involves MePCE and LARP7.

Purpose of the Study:

  • To investigate the function of MePCE on chromatin, specifically in DNA double-stranded break (DSB) repair.
  • To elucidate the interaction of MePCE with R-loop processing and DNA repair factors.
  • To understand the role of MePCE in the context of 7SK RNPc dynamics at DSBs.

Main Methods:

  • Investigated MePCE recruitment to DSBs.
  • Assessed the impact of MePCE depletion on homologous recombination (HR) repair.
  • Analyzed RAD51 loading and R-loop levels at DSBs.
  • Examined interactions with R-loop processing factors and LARP7.

Main Results:

  • MePCE is recruited to DSBs and interacts with DNA repair factors.
  • MePCE depletion impairs HR, reduces RAD51 loading, and increases R-loop levels at DSBs.
  • MePCE depletion alters LARP7 interaction with R-loops, leading to its degradation by BRCA1/BARD1.
  • Dynamic regulation of 7SK RNPc at DSBs was uncovered.

Conclusions:

  • MePCE plays a crucial role in DSB repair by homologous recombination.
  • MePCE's function at DSBs involves R-loop processing and interaction with BRCA1/BARD1 pathway.
  • These findings explain the synthetic lethality observed between MePCE and BRCA1 deficiency.