• Publications
  • Influence
Rapid and efficient site-specific mutagenesis without phenotypic selection.
  • T. Kunkel
  • Biology, Medicine
  • Proceedings of the National Academy of Sciences…
  • 1985
TLDR
The high efficiency, approximately equal to 10-fold greater than that observed using current methods without enrichment procedures, is obtained by using a DNA template containing several uracil residues in place of thymine, which is applied to mutations introduced via both oligonucleotides and error-prone polymerization. Expand
Incidence and functional consequences of hMLH1 promoter hypermethylation in colorectal carcinoma.
TLDR
The results suggest that microsatellite instability in sporadic colorectal cancer often results from epigenetic inactivation of hMLH1 in association with DNA methylation. Expand
DNA Replication Fidelity*
  • T. Kunkel
  • Biology, Medicine
  • Journal of Biological Chemistry
  • 23 April 2004
TLDR
Current understanding of replication fidelity is reviewed, with emphasis on structural and biochemical studies of DNA polymerases that provide new insights into the importance of hydrogen bonding, base pair geometry, and substrate-induced conformational changes to fidelity. Expand
Abundant ribonucleotide incorporation into DNA by yeast replicative polymerases
TLDR
Measurements of nucleoside triphosphate levels in Saccharomyces cerevisiae reveal that the four rNTPs are in 36- to 190-fold molar excess over their corresponding dNTBs, consistent with the possibility that more than 10,000 rNMPs may be incorporated into the nuclear genome during each round of replication in yeast. Expand
Genome instability due to ribonucleotide incorporation into DNA
TLDR
The data indicate that ribonucleotides are incorporated during replication in vivo, that they are removed by RNase H2-dependent repair, and that defective repair results in replicative stress and genome instability via DNA strand misalignment. Expand
DNA mismatch repair.
TLDR
This review focuses on the biochemical mechanism of MMR replication errors, on structure-function studies of MMR proteins, on how mismatches are recognized, on the process by which the newly replicated strand is identified, and on excision of the replication error. Expand
Requirement for PCNA in DNA Mismatch Repair at a Step Preceding DNA Resynthesis
TLDR
The data suggest a PCNA requirement in mismatch repair at a step preceding DNA resynthesis in yeast and human expression libraries, and the ability of PCNA to bind to MLH1 and MSH2 may reflect linkage between mismatch repair and replication. Expand
Human chromosome 3 corrects mismatch repair deficiency and microsatellite instability and reduces N-methyl-N'-nitro-N-nitrosoguanidine tolerance in colon tumor cells with homozygous hMLH1 mutation.
TLDR
The hypothesis that mutations in both alleles of the hMLH1 gene are necessary for the manifestation of defective mismatch repair and microsatellite instability and for enhanced MNNG tolerance is supported. Expand
Fidelity of DNA synthesis by the Thermus aquaticus DNA polymerase.
TLDR
The fidelity of in vitro DNA synthesis catalyzed at high temperature by the DNA polymerase from the thermophilic bacterium Thermus aquaticus is determined and it is demonstrated that the purified polymerase lacks detectable exonucleolytic proofreading activity. Expand
Functional Interaction of Proliferating Cell Nuclear Antigen with MSH2-MSH6 and MSH2-MSH3 Complexes*
TLDR
It is reported that MSH3 and MSH6, but not MSH2, contain N-terminal sequence motifs characteristic of proteins that bind to PCNA, which may facilitate early steps in DNA mismatch repair and may also be important for other roles of these eukaryotic MutS homologs. Expand
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