FTO regulates the DNA damage response via effects on cell-cycle progression

Area of Science:

• Molecular Biology
• Genetics
• Cancer Research

Background:

• The fat mass and obesity-associated protein (FTO) is an N6-methyladenosine demethylase involved in tumorigenesis.
• FTO's role in DNA damage response (DDR) and its mechanisms remain poorly understood.

Purpose of the Study:

• To investigate the role of FTO in DNA damage response.
• To elucidate the underlying mechanisms of FTO's involvement in DDR.

Main Methods:

• FTO gene knockout in TK6 cells using CRISPR/Cas9.
• Genotoxicity assays (micronucleus, TK mutation assays).
• RNA sequencing, western blotting, qRT-PCR, and flow cytometry analysis.

Main Results:

• FTO knockout cells exhibited increased genotoxicity upon exposure to DNA damaging agents.
• FTO deletion disrupted the p38 MAPK pathway and nucleotide excision repair.
• FTO deficiency impaired G2/M cell cycle arrest following DNA damage treatment.

Conclusions:

• FTO plays a significant role in DNA damage response.
• FTO acts by influencing DNA repair pathways and cell cycle progression.
• FTO deficiency exacerbates genotoxicity, suggesting its tumor-suppressive function in DDR.