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Related Concept Videos

Homologous Recombination02:31

Homologous Recombination

56.3K
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...
56.3K
Mismatch Repair01:20

Mismatch Repair

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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.
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
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Related Experiment Video

Updated: Oct 23, 2025

Identifying the Effects of BRCA1 Mutations on Homologous Recombination using Cells that Express Endogenous Wild-type BRCA1
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Identifying the Effects of BRCA1 Mutations on Homologous Recombination using Cells that Express Endogenous Wild-type BRCA1

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Utility of Homologous Recombination Deficiency Biomarkers Across Cancer Types.

Shiro Takamatsu1, J B Brown2,3, Ken Yamaguchi1

  • 1Department of Gynecology and Obstetrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

JCO Precision Oncology
|August 23, 2021
PubMed
Summary

Homologous recombination deficiency (HRD) is linked to DNA repair and impacts chemotherapy sensitivity across various cancers. This study expands HRD analysis to all tumor types, improving treatment decisions for precision oncology.

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Heterogeneity Mapping of Protein Expression in Tumors using Quantitative Immunofluorescence
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Area of Science:

  • Genomic instability and DNA repair mechanisms in oncology.
  • Pan-cancer genomic analysis and biomarker discovery.

Background:

  • Homologous recombination DNA repair deficiency (HRD) predicts sensitivity to platinum-based chemotherapy and PARP inhibitors in specific cancers like breast and ovarian.
  • BRCA1/2 alterations and genomic scars are established HRD biomarkers, but the role of other HRR genes across all cancer types remains under-investigated.

Purpose of the Study:

  • To comprehensively analyze homologous recombination repair (HRR) pathway gene alterations and their clinical significance across all solid tumor types.
  • To investigate the association between HRR gene alterations, genomic scar scores (HRD score, mutational signature 3 ratio), and sensitivity to DNA-damaging agents.
  • To evaluate the utility of pan-cancer HRD analysis for improving chemotherapy decision-making in precision oncology.

Main Methods:

  • Utilized The Cancer Genome Atlas and Cancer Cell Line Encyclopedia datasets for comprehensive analysis of solid tumors.
  • Assessed HRR pathway gene alterations, loss-of-heterozygosity, HRD scores, mutational signatures, DNA methylation, gene expression, TP53 mutations, and clinical/in vitro drug response.
  • Investigated the influence of sex and TP53 mutation status on the relationship between HRR alterations and genomic scars.

Main Results:

  • Biallelic alterations in non-BRCA1/2 HRR genes correlated with elevated genomic scar scores.
  • The association between HRR alterations and genomic scars varied significantly by sex and TP53 mutation status.
  • HRD-determined tumors exhibited distinct gene expression profiles and significantly higher sensitivity to DNA-damaging agents compared to non-HRD tumors.

Conclusions:

  • HRD analysis is valuable across all cancer types, offering improved chemotherapy decision-making and efficacy.
  • This pan-cancer approach represents a significant advancement in precision oncology by broadening the application of HRD biomarkers.
  • The findings support the expanded use of HRD assessment for personalized cancer treatment strategies.