DNA polymerases ζ and Rev1 mediate error-prone bypass of non-B DNA structures

Area of Science:

• Molecular Biology
• Genetics
• Biochemistry

Background:

• DNA polymerase ζ (Pol ζ) and Rev1 are crucial for translesion DNA synthesis.
• Pol ζ can also replicate undamaged DNA when the normal replisome is impaired.

Purpose of the Study:

• To define replication disturbances triggering error-prone polymerases without DNA damage.
• To describe the roles of Rev1 and Pol ζ in handling these disturbances.

Main Methods:

• Investigated mutations at replication stalling sites.
• Analyzed the roles of Rev1 and Pol ζ in hairpin bypass.
• Examined postreplicative pathways involving PCNA ubiquitylation.

Main Results:

• Pol ζ/Rev1-dependent mutations occur at stalled replication forks in hairpin-forming sequences.
• Rev1 incorporates a 'C' at hairpin bases; Pol ζ extends mismatched termini after template switching.
• A backup pathway involving PCNA ubiquitylation ensures accurate bypass when Pol ζ/Rev1 is inactive.

Conclusions:

• Noncanonical DNA structures significantly influence mutagenesis.
• A mechanism for complex mutations, a Pol ζ signature, involving hairpin bypass has been elucidated.