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SPIN1 facilitates chemoresistance and HR repair by promoting Tip60 binding to H3K9me3

Yukun Wang1, Mengyao Li1, Yuhan Chen1

  • 1College of Life Sciences, Hebei University, Baoding, Hebei Province, 071002, China.

EMBO Reports
|August 1, 2024
PubMed

Insights

Spindlin1 (SPIN1) aids homologous recombination (HR) DNA repair by binding Poly-ADP-ribose (PAR) and promoting H3K9me3 accumulation. This mechanism enhances chemoresistance, revealing SPIN1

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Epigenetics

Background:

  • Spindlin1 (SPIN1), a transcriptional coactivator, has known roles in development and cancer.
  • Its specific involvement in DNA damage repair pathways was previously uncharacterized.

Purpose of the Study:

  • To elucidate the role of SPIN1 in DNA damage repair mechanisms.
  • To investigate SPIN1's function in homologous recombination (HR) and its impact on chemoresistance.

Main Methods:

  • Investigated SPIN1 recruitment to DNA lesions via its N-terminal disordered region.
  • Assessed SPIN1's interaction with Poly-ADP-ribose (PAR) and its effect on H3K9me3 accumulation.
  • Examined the influence of SPIN1 on ATM activation and HR repair efficiency.

Main Results:

  • SPIN1 is recruited to DNA lesions by binding to Poly-ADP-ribose (PAR).
  • SPIN1 facilitates homologous recombination (HR) repair by promoting H3K9me3 accumulation and Tip60 interaction.
  • SPIN1 enhances ATM activation and increases chemoresistance.

Conclusions:

  • SPIN1 plays a novel role in activating H3K9me3-dependent DNA repair pathways.
  • SPIN1's modulation of double-strand break (DSB) repair efficiency may contribute to cancer chemoresistance.
Keywords:
ATMDNA Damage RepairH3K9me3SPIN1Tip60

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