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PTEN in the maintenance of genome integrity: From DNA replication to chromosome segregation

Sheng-Qi Hou1, Meng Ouyang1, Andrew Brandmaier1

  • 1Department of Radiation Oncology, Weill Cornell Medicine, Cornell University, New York, NY, USA.

Bioessays : News and Reviews in Molecular, Cellular and Developmental Biology
|September 12, 2017
PubMed

Insights

The tumor suppressor PTEN (Phosphatase and tensin homolog) is crucial for accurate DNA replication and chromosome segregation. Loss of PTEN function leads to genomic instability and cancer development.

Area of Science:

  • Genetics
  • Molecular Biology
  • Cancer Biology

Background:

  • Faithful DNA replication and chromosome segregation are vital for genetic transmission.
  • Disruptions in these processes, often due to tumor suppressor loss, are hallmarks of cancer.
  • PTEN (Phosphatase and tensin homolog) is a key tumor suppressor frequently altered in human cancers, with its loss linked to aneuploidy and poor prognosis.

Purpose of the Study:

  • To summarize the current understanding of PTEN's role in high-fidelity genetic information transmission.
  • To discuss PTEN-mediated pathways involved in genome maintenance.
  • To highlight potential therapeutic targets for cancer treatment related to PTEN function.

Main Methods:

  • Literature review and synthesis of existing research on PTEN function in genome stability.
  • Analysis of studies investigating the consequences of PTEN loss or mutation in cancer and preclinical models.
  • Identification of pathways regulated by PTEN that impact DNA replication, stress response, and chromosome segregation.

Main Results:

  • PTEN deficiency induces DNA replication stress and confers cellular stress tolerance.
  • Loss of PTEN disrupts mitotic spindle architecture, leading to chromosome instability (both numerical and structural).
  • PTEN actively guards the genome by regulating multiple aspects of chromosome inheritance.

Conclusions:

  • PTEN plays a critical role in maintaining genomic integrity through its control over DNA replication and chromosome segregation.
  • Understanding PTEN's genome maintenance functions offers potential avenues for novel cancer therapies.
  • Targeting PTEN pathways could be a promising strategy for treating cancers with PTEN alterations.
Keywords:
DNA replicationPTENcheckpointchromosome segregationgenomemitotic spindle

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