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The Arp2/3 inhibitory protein Arpin inhibits homology-directed DNA repair

Gleb Simanov1, Nathalie Rocques1, Stéphane Romero1

  • 1Laboratory of Structural Biology of the Cell (BIOC), UMR7654 CNRS/Ecole polytechnique, Institut Polytechnique de Paris, Palaiseau, France.

Biology of the Cell
|August 9, 2024
PubMed
Abstract

Insights

Arpin loss enhances cell migration and DNA repair. This protein regulates lamellipodial protrusions in the cytosol and homologous DNA repair (HDR) in the nucleus, impacting cancer progression.

Area of Science:

  • Cell biology
  • Cancer research
  • Molecular genetics

Background:

  • Arpin is an Arp2/3 inhibitory protein that suppresses lamellipodial protrusions and cell migration.
  • Loss of Arpin expression is observed in several cancer types, suggesting a role in tumorigenesis.

Purpose of the Study:

  • To investigate the role of Arpin in DNA damage response and repair.
  • To explore the correlation between Arpin levels and DNA damage response markers in human mammary carcinomas.

Main Methods:

  • Reverse Phase Protein Array (RPPA) analysis of Arpin and DNA damage response markers in human mammary carcinomas.
  • Assessment of double-strand break (DSB) clustering in Arpin-null cells treated with DNA damaging agents.
  • Utilizing a specific homologous DNA repair (HDR) assay to quantify repair efficiency upon Arpin depletion.

Main Results:

  • Arpin protein levels positively correlated with several DNA damage response markers.
  • Arpin-null cells exhibited enhanced DSB clustering following DNA damage treatment.
  • Arpin depletion resulted in a two-fold increase in HDR efficiency, attributed to Arp2/3 complex inactivation.

Conclusions:

  • Arpin plays a dual role, regulating cell migration in the cytosol and homologous DNA repair (HDR) in the nucleus.
  • Loss of Arpin expression coordinates increased cell migration with heightened DNA repair capacity, potentially linked to DNA damage induced by cell motility.
Keywords:
Arp2/3ArpinDNA repairdouble‐strand breakshomology‐directed repair

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