Journal article
Human DNA polymerase κ uses template–primer misalignment as a novel means for extending mispaired termini and for generating single-base deletions
Genes & development, Vol.17(17), pp.2191-2199
09/01/2003
DOI: 10.1101/gad.1108603
PMCID: PMC196459
PMID: 12952891
Abstract
Human DNA polymerase κ (hPolκ) is a proficient extender of
mispaired primer termini on undamaged DNA, wherein it extends directly by
incorporating the next correct nucleotide, generating single-base
substitutions in the process. Biochemical and genetic studies, however, have
indicated that, in addition to single-base substitutions, Polκ generates
single-base deletions. Here we show that hPolκ is very adept at using
template–primer misalignment as a novel means for extending mispaired
termini and for generating single-base deletions. The proficient ability of
hPolκ to extend mispaired primer termini either directly or by
misalignment could be important for the continued and efficient progression of
the replication fork when mismatches introduced by the replicative polymerase
are not proofread. In extending from nucleotides opposite DNA lesions,
hPolκ uses the direct and misalignment modes of mispair extension to
different extents, depending on whether the template base is present or not at
the primer terminus; thus, although hPolκ can extend directly from
nucleotides opposite damaged bases, it can use only the misalignment mechanism
to extend from nucleotides opposite an abasic site. A particularly
unconstrained active site at the template–primer junction could afford
hPolκ the ability to tolerate the geometric distortions of mismatched
base pairs or those resulting from template–primer misalignment, thereby
enabling it to use both of these modes of mispair extension.
Details
- Title: Subtitle
- Human DNA polymerase κ uses template–primer misalignment as a novel means for extending mispaired termini and for generating single-base deletions
- Creators
- William T Wolfle - Sealy Center for Molecular Science, University of Texas Medical Branch at Galveston, Galveston, Texas 77555-1061, USAM. Todd Washington - Sealy Center for Molecular Science, University of Texas Medical Branch at Galveston, Galveston, Texas 77555-1061, USALouise Prakash - Sealy Center for Molecular Science, University of Texas Medical Branch at Galveston, Galveston, Texas 77555-1061, USASatya Prakash - Sealy Center for Molecular Science, University of Texas Medical Branch at Galveston, Galveston, Texas 77555-1061, USA
- Resource Type
- Journal article
- Publication Details
- Genes & development, Vol.17(17), pp.2191-2199
- Publisher
- Cold Spring Harbor Laboratory Press
- DOI
- 10.1101/gad.1108603
- PMID
- 12952891
- PMCID
- PMC196459
- ISSN
- 0890-9369
- eISSN
- 1549-5477
- Language
- English
- Date published
- 09/01/2003
- Academic Unit
- Radiation Oncology; Biochemistry and Molecular Biology
- Record Identifier
- 9984025261702771
Metrics
17 Record Views