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Mutations for Worse or Better: Low Fidelity DNA Synthesis by SOS DNA Polymerase V is a Tightly‐Regulated Double‐Edged Sword
Author(s) -
Goodman Myron,
Erdem Aysen,
Jaszczur Malgorzata,
Bertram Jeffrey,
Woodgate Roger,
Cox Michael
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.108.3
Subject(s) - dna polymerase , biology , dna replication , dna polymerase ii , genetics , dna clamp , polymerase , dna , microbiology and biotechnology , polymerase chain reaction , gene , reverse transcriptase
Mutations are almost always bad typically with negative consequences. But mutations can also be good by serving as the engine driving evolution. A specialized DNA polymerase (pol) family, the Y‐family, is present spanning bacteria to humans, whose central role is to copy past damaged DNA template bases that block replication. There's no free lunch however, because the costs of fully replicating the genome are often mutations frequently targeted at lesion sites, but occasionally occurring within undamaged template regions. The “error‐prone” DNA polymerase V, is induced in response to DNA damage by the Escherichia coli SOS regulon, and is responsible for the lion's share of chromosomal mutations by copying past aberrant template bases. We will discuss the great lengths to which the cell goes to limit the access of pol V to work just in the vicinity of damaged DNA by imposing tight regulation temporally, spatially in the cell, and internally within pol V. The key self‐regulatory feature centers on the recent surprising discovery that the polymerase contains an intrinsic DNA‐dependent ATPase activity. We will discuss how ATP and ATP hydrolysis conspire to determine how and when the polymerase is activated, allowing it to bind to DNA and perform translesion synthesis, and then deactivated, causing its release from DNA.