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Carcinogenesis caused by transcription-coupled DNA damage through GANP and other components of the TREX-2 complex

Yasuhiro Sakai1,2, Kazuhiko Kuwahara3

  • 1Department of Tumor Pathology, Hamamatsu University School of Medicine, Shizuoka, Japan.

Pathology International
|February 27, 2024
PubMed

Insights

The transcription-export-2 (TREX-2) complex, particularly GANP, drives DNA damage linked to cancer. Aberrant TREX-2 expression predicts cancer prognosis and chemotherapy response.

Area of Science:

  • Molecular Biology
  • Immunology
  • Oncology

Background:

  • Gene perturbation is crucial for antibody affinity maturation but can also cause cancer.
  • Transcription can lead to DNA damage and genomic instability.
  • The mammalian transcription-export-2 (TREX-2) complex, including GANP, is increasingly studied for its role in cellular processes.

Purpose of the Study:

  • To review the role of the TREX-2 complex in transcription-coupled DNA damage.
  • To explore the link between GANP, antibody affinity maturation, and cancer etiology.
  • To highlight the association of TREX-2 components with various cancers and their prognostic value.

Main Methods:

  • Review of existing literature on mRNA nuclear export and transcription-coupled DNA damage.
  • Examination of the immunological relationship between GANP and antibody affinity maturation.
  • Analysis of studies linking TREX-2 complex expression to carcinogenesis, lymphomagenesis, and teratomagenesis.

Main Results:

  • The TREX-2 complex, especially GANP, is implicated in DNA damage during transcription.
  • GANP plays a role in antibody affinity maturation.
  • Aberrant expression of TREX-2 components, notably GANP, correlates with solid tumors, lymphomas, and testicular teratomas.

Conclusions:

  • The TREX-2 complex, particularly GANP, contributes to cancer development through transcription-coupled DNA damage.
  • TREX-2 components are potential biomarkers for cancer prognosis and predicting treatment efficacy.
Keywords:
breast cancer susceptibility gene 2carcinogenesisdeleted in split hand/split foot 1germinal center-associated nuclear proteinhomologous recombination repairlymphomagenesismRNA nuclear exportteratomagenesistranscription-coupled DNA damagetranscription-export-2 complex

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