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Updated: Jul 26, 2025

Examination of Proteins Bound to Nascent DNA in Mammalian Cells Using BrdU-ChIP-Slot-Western Technique
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Chromatin-Associated SIN3B Protects Cancer Cells from Genotoxic Stress-Induced Apoptosis and Dictates DNA Damage

Jorge Morales-Valencia1,2, Coralie Petit1, Alexander Calderon1

  • 1Department of Biochemistry and Molecular Pharmacology, NYU Langone Medical Center, New York, New York.

Molecular Cancer Research : MCR
|June 14, 2023
PubMed

Insights

The scaffolding protein SIN3B is crucial for DNA repair and genomic integrity. Its inactivation delays double-strand break resolution and sensitizes cancer cells to chemotherapy, revealing a new therapeutic target.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Genomics

Background:

  • Transcription and DNA damage repair are coordinated processes.
  • SIN3B is a known transcriptional co-repressor of cell cycle genes.
  • The role of SIN3B in DNA damage response was previously unknown.

Purpose of the Study:

  • To investigate the function of SIN3B in the DNA damage response.
  • To determine the effect of SIN3B inactivation on DNA repair.
  • To explore the therapeutic potential of targeting SIN3B in cancer.

Main Methods:

  • Assessing DNA double-strand break resolution after SIN3B inactivation.
  • Evaluating cancer cell sensitivity to DNA-damaging agents (cisplatin, doxorubicin).
  • Investigating SIN3B recruitment to DNA damage sites and its interaction with MDC1.
  • Analyzing the impact of SIN3B inactivation on DNA repair pathway choice (NHEJ).

Main Results:

  • SIN3B inactivation delays DNA double-strand break resolution.
  • Loss of SIN3B sensitizes cancer cells to chemotherapy drugs.
  • SIN3B is recruited to DNA damage sites and recruits MDC1.
  • SIN3B inactivation promotes alternative NHEJ over canonical NHEJ.

Conclusions:

  • SIN3B acts as a gatekeeper of genomic integrity.
  • SIN3B influences the choice of DNA repair pathways.
  • Targeting SIN3B chromatin-modifying complexes presents a novel therapeutic vulnerability in cancer.

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