Oncoprotein Tudor-SN is a key determinant providing survival advantage under DNA damaging stress

Xiao Fu1, Chunyan Zhang1, Hao Meng1

  • 1Key Laboratory of Immune Microenvironment and Disease, Ministry of Education, Key Laboratory of Cellular and Molecular Immunology in Tianjin, Department of Biochemistry and Molecular Biology, Excellent Talent Project, Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, 300070, Tianjin, China.

Insights

Tudor-SN protein is crucial for early DNA damage response by recruiting repair factors and promoting cell survival. Its dysfunction impairs DNA repair, suggesting a role in cancer radioresistance.

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Biochemistry

Background:

  • DNA damage response (DDR) is essential for maintaining genomic integrity.
  • Tudor-SN is a protein implicated in cellular processes, but its specific role in DDR is not fully understood.

Purpose of the Study:

  • To elucidate the function of Tudor-SN in the early stages of DNA damage response.
  • To investigate the molecular mechanisms by which Tudor-SN participates in DDR and cell survival.

Main Methods:

  • Utilized X-ray and laser irradiation to induce DNA damage in cellular models.
  • Investigated protein-protein interactions using techniques such as co-immunoprecipitation.
  • Assessed chromatin structure changes and DNA repair pathway activation via molecular assays.

Main Results:

  • Tudor-SN accumulates at DNA damage sites in a poly(ADP-ribosyl)ation-dependent manner, interacting with PARP-1 via its SN domain.
  • Tudor-SN recruits SMARCA5 and GCN5 to damage sites, leading to chromatin relaxation and ATM kinase activation.
  • Loss-of-function of Tudor-SN resulted in impaired chromatin relaxation, reduced recruitment of repair factors, and deficiencies in DNA repair and cell survival.

Conclusions:

  • Tudor-SN is a key regulator of the early DNA damage response, orchestrating chromatin remodeling and activating repair pathways.
  • Tudor-SN's role in promoting cell survival after DNA damage highlights its potential involvement in cancer radioresistance due to its high expression in tumors.

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