Regulation of error-prone translesion synthesis by Spartan/C1orf124

Area of Science:

• Molecular Biology
• Genetics
• Biochemistry

Background:

• Translesion synthesis (TLS) bypasses DNA damage using low-fidelity polymerases, potentially causing mutations.
• Regulatory mechanisms controlling TLS-associated mutagenesis are not fully understood.
• The PCNA-binding protein Spartan was previously implicated in suppressing DNA damage-induced mutagenesis.

Purpose of the Study:

• To investigate the role of Spartan in regulating error-prone TLS.
• To identify the molecular mechanisms by which Spartan suppresses mutagenesis.
• To elucidate Spartan's interaction with key TLS factors.

Main Methods:

• Depletion of Spartan protein in cellular models.
• Analysis of DNA damage-induced mutagenesis.
• Co-immunoprecipitation assays to study protein interactions.
• Investigating the interaction between Spartan and POLD3.

Main Results:

• Spartan negatively regulates error-prone TLS dependent on POLD3.
• The SprT domain of Spartan directly interacts with POLD3.
• Spartan depletion leads to POLD3 complex formation with Rev1 and Pol ζ, increasing mutagenesis.
• Spartan suppresses damage-induced mutagenesis by inhibiting POLD3 function in Rev1/Pol ζ-dependent TLS.

Conclusions:

• Spartan acts as a negative regulator of error-prone TLS.
• Spartan's SprT domain is crucial for suppressing POLD3-mediated mutagenesis.
• This study reveals a novel regulatory mechanism controlling Rev1/Pol ζ-dependent TLS.