T-T cyclobutane dimers are misinstructive, rather than non-instructive, mutagenic lesions

Area of Science:

• Molecular Biology
• Genetics
• Microbiology

Background:

• SOS-induced DNA lesions in Escherichia coli are often termed nonpairing or non-instructive.
• The suitability of these terms for all lesions, such as cyclobutane dimers, is debated.

Purpose of the Study:

• To investigate the mutagenic properties of cyclobutane dimers and abasic sites in Escherichia coli.
• To determine if cyclobutane dimers are misinstructive or non-instructive lesions.

Main Methods:

• Comparison of error frequencies and spectra using single-stranded vectors with specific DNA lesions.
• Analysis of replication fidelity across T-T sequences containing cis-syn or trans-syn cyclobutane dimers or abasic sites.

Main Results:

• Replication accuracy with dimer-containing templates is not due to polymerase preference for dAMP insertion.
• Mispairing, rather than non-pairing, is the primary cause of mutations at these lesions.
• Cyclobutane dimers function as misinstructive lesions.

Conclusions:

• Cyclobutane dimers are misinstructive, challenging the 'non-instructive' classification.
• The common characteristic of SOS-inducing lesions is their replication-blocking ability, not an inability to form base pairs.