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The DNTTIP1-PARP1 interaction orchestrates MiDAC recruitment and activity for NHEJ-mediated genome stability

Yan Qin1, Yanhui Ma1, Ao Wei1

  • 1Key Laboratory of Breast Cancer Prevention and Therapy (Ministry of Education), Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, China.

The Journal of Biological Chemistry
|July 16, 2026
PubMed

Insights

Poly(ADP-ribose) polymerase 1 (PARP1) directs the Mitotic Deacetylase Complex (MiDAC) to DNA damage sites via physical interaction with DNTTIP1, independent of PARylation activity. This interaction is crucial for DNA repair and genome stability.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • The Mitotic Deacetylase Complex (MiDAC) is vital for DNA damage response (DDR).
  • Mechanisms of MiDAC recruitment to double-strand breaks (DSBs) are not fully understood.

Purpose of the Study:

  • To elucidate the mechanism of MiDAC recruitment to DSBs.
  • To identify key factors involved in MiDAC-mediated DNA repair.

Main Methods:

  • Investigated the interaction between PARP1 and MiDAC components.
  • Utilized biochemical assays and cell-based experiments to assess MiDAC recruitment and function.
  • Analyzed histone modifications and DNA repair efficiency upon disruption of the PARP1-DNTTIP1 interaction.

Main Results:

  • Identified PARP1 as the crucial factor for MiDAC recruitment to DSBs, dependent on its physical presence, not PARylation activity.
  • Demonstrated a direct interaction between the MiDAC subunit DNTTIP1 and PARP1.
  • Disruption of the PARP1-DNTTIP1 interaction impaired MiDAC recruitment, H2AK5ac/K9ac deacetylation, and led to genome instability.
  • Showed the PARP1-DNTTIP1 interaction is essential for non-homologous end joining (NHEJ) complex assembly and function, impacting immunoglobulin class switch recombination (CSR).

Conclusions:

  • Established the PARP1-DNTTIP1 axis as a critical regulator of MiDAC recruitment and function in a PARylation-independent manner.
  • Linked early DNA damage sensing to chromatin remodeling and efficient DSB repair.
  • Highlighted the importance of this axis for genome stability and B cell function.
Keywords:
CSRDDRMiDACNHEJPARP1

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