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The two-step model for translesion synthesis: then and now
1MRC Cell Mutation Unit, University of Sussex, Falmer, Brighton BN1 9RR, UK. b.a.bridges@susx.ac.uk
Mutation Research
|May 9, 2001
Summary
Bacterial DNA polymerase V, previously UmuD(2)' UmuC, performs both base misincorporation and bypass during translesion synthesis. This clarifies its role in DNA repair and mutation formation after UV exposure.
Area of Science:
- Molecular Biology
- Genetics
- Biochemistry
Background:
- Base substitution mutations arise during translesion synthesis (TLS) opposite DNA lesions.
- The UmuD(2)\' UmuC complex, crucial for TLS, is upregulated in SOS-induced bacterial cells.
Observation:
- The original "two-step" model proposed separate steps for misincorporation and bypass.
- Initially, UmuD(2)\' UmuC was thought to be involved only in bypass, with other polymerases handling misincorporation.
Findings:
- The UmuD(2)\' UmuC complex is identified as DNA polymerase V, capable of both misincorporation and bypass in vitro.
- DNA polymerase III plays an accessory role in vitro and potentially in vivo, though its exact function is unclear.
- DNA polymerases II and IV are also upregulated during SOS response, suggesting broader involvement in TLS.
Implications:
- The bacterial replication factory may involve a dynamic interplay of up to five DNA polymerases.
- Protein-protein interactions could facilitate a "cassette system" for polymerase selection during DNA replication and repair.
- The revised understanding of DNA polymerase V function refines models of mutagenesis and DNA repair mechanisms.