Abstract
Human DNA polymerase theta (pol θ or POLQ) is a proofreading-deficient family A enzyme implicated in translesion synthesis (TLS) and perhaps in somatic hypermutation (SHM) of immunoglobulin genes. These proposed functions and kinetic studies imply that pol θ may synthesize DNA with low fidelity. Here, we show that when copying undamaged DNA, pol θ generates single base errors at rates 10- to more than 100-fold higher than for other family A members. Pol θ adds single nucleotides to homopolymeric runs at particularly high rates, exceeding 1% in certain sequence contexts, and generates single base substitutions at an average rate of 2.4 × 103, comparable to inaccurate family Y human pol κ (5.8 ×103) also implicated in TLS. Like pol BA; pol θ is processive, implying that it may be tightly regulated to avoid deleterious mutagenesis. Pol θ also generates certain base substitutions at high rates within sequence contexts similar to those inferred to be copied by pol θ during SHM of immunoglobulin genes in mice. Thus, pol θ is an exception among family A polymerases, and its low fidelity is consistent with its proposed roles in TLS and SHM.
Original language | English (US) |
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Pages (from-to) | 3847-3856 |
Number of pages | 10 |
Journal | Nucleic acids research |
Volume | 36 |
Issue number | 11 |
DOIs | |
State | Published - Jun 2008 |
Externally published | Yes |
ASJC Scopus subject areas
- Genetics