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ZSCAN4 interacts with PARP1 to promote DNA repair in mouse embryonic stem cells

Li-Kuang Tsai1, Min Peng1, Chia-Chun Chang1

  • 1Institute of Biotechnology, National Taiwan University, Taipei, 106, Taiwan, ROC.

Cell & Bioscience
|October 24, 2023
PubMed
Abstract

Insights

Zinc finger and SCAN domain containing 4 (ZSCAN4) aids DNA repair by interacting with Poly (ADP-ribose) polymerase 1 (PARP1). This protein-protein interaction in mouse embryonic stem cells reduces DNA double strand breaks, enhancing genome stability.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cell Biology

Background:

  • Eukaryotic DNA double-strand breaks (DSB) are repaired via canonical non-homologous end joining (c-NHEJ), homologous recombination (HR), and alternative NHEJ (alt-NHEJ).
  • Zinc finger and SCAN domain containing 4 (ZSCAN4) is sporadically expressed in mouse embryonic stem cells (mESCs) and known to promote HR for genome stability.

Purpose of the Study:

  • To investigate the role of ZSCAN4 in DNA repair pathways, specifically its interaction with Poly (ADP-ribose) polymerase 1 (PARP1).
  • To elucidate the molecular mechanisms underlying ZSCAN4's contribution to genome stability.

Main Methods:

  • Investigated ZSCAN4's role in DNA repair in mESCs.
  • Utilized PARP1 inhibition via small molecule inhibitors and gene knockout.
  • Performed co-immunoprecipitation to assess PARP1-ZSCAN4 binding.

Main Results:

  • ZSCAN4 promotes DNA repair through association with PARP1, a key component of the alt-NHEJ pathway.
  • ZSCAN4-expressing mESCs exhibit reduced DNA double-strand breaks (DSBs) compared to ZSCAN4-negative cells.
  • The reduction in DSBs mediated by ZSCAN4 is dependent on PARP1 activity, as inhibition of PARP1 abolishes this effect.
  • PARP1 directly binds to ZSCAN4, with specific domains (second α-helix and fourth zinc finger) being critical for this interaction.

Conclusions:

  • ZSCAN4 and PARP1 interact directly at the protein level.
  • This interaction reveals a novel molecular mechanism by which ZSCAN4 contributes to the reduction of DSBs in mESCs, highlighting its role in DNA repair beyond HR.
Keywords:
DNA double strand breaksMouse embryonic stem cellsPARP1ZSCAN4

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