Low-fidelity DNA synthesis by human DNA polymerase theta.

Abstract:

Human DNA polymerase theta (pol 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 may synthesize DNA with low fidelity. Here, we show that when copying undamaged DNA, pol generates single base errors at rates 10- to more than 100-fold higher than for other family A members. Pol 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 x 10(-3), comparable to inaccurate family Y human pol kappa (5.8 x 10(-3)) also implicated in TLS. Like pol kappa, pol is processive, implying that it may be tightly regulated to avoid deleterious mutagenesis. Pol also generates certain base substitutions at high rates within sequence contexts similar to those inferred to be copied by pol during SHM of immunoglobulin genes in mice. Thus, pol is an exception among family A polymerases, and its low fidelity is consistent with its proposed roles in TLS and SHM.

Polymerases:

Topics:

Fidelity, Historical Protein Properties (MW, pI, ...), Exonuclease Activity, Source / Purification

Status:

new topics/pols set partial results complete validated

Results:

Polymerase Reference Property Result Context
Human Pol theta Arana ME2008 Molecular Weight 290kD
Human Pol theta Arana ME2008 3-5' Exonuclease (proofreading) No
Human Pol theta Arana ME2008 Overall Error Rate 0.0014 errors/bp Technique: M13mp2 forward mutation assay (Single base deletions)
Human Pol theta Arana ME2008 Overall Error Rate 0.0033 errors/bp Technique: M13mp2 forward mutation assay (Single base additions)
Human Pol theta Arana ME2008 Nucleotide Substitution Rate 0.0024 errors/bp Technique: M13mp2 forward mutation assay
Human Pol theta Arana ME2008 Full length or truncated Full length

Entry validated by:

Log in to edit reference All References

Using Polbase tables:

Sorting:

Tables may be sorted by clicking on any of the column titles. A second click reverses the sort order. <Ctrl> + click on the column titles to sort by more than one column (e.g. family then name).

Filtering:

It is also possible to filter the table by typing into the search box above the table. This will instantly hide lines from the table that do not contain your search text.