The human gastric cancer-associated DNA polymerase β variant D160N is a mutator that induces cellular transformation

Katherine A. Donigan, Suzanne E. Hile, Kristin Eckert, Joann B. Sweasy

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Approximately 30% of human tumors sequenced to date harbor mutations in the POLB gene that are not present in matched normal tissue. Many mutations give rise to enzymes that contain non-synonymous single amino acid substitutions, several of which have been found to have aberrant activity or fidelity and transform cells when expressed. The DNA Polymerase β (Pol β) variant Asp160Asn (D160N) was first identified in a gastric tumor. Expression of D160N in cells induces cellular transformation as measured by hyperproliferation, focus formation, anchorage-independent growth and invasion. Here, we show that D160N is an active mutator polymerase that induces complex mutations. Our data support the interpretation that complex mutagenesis is the underlying mechanism of the observed cellular phenotypes, all of which are linked to tumorigenesis or tumor progression.

Original languageEnglish (US)
Pages (from-to)381-390
Number of pages10
JournalDNA Repair
Volume11
Issue number4
DOIs
StatePublished - Apr 1 2012

Fingerprint

DNA-Directed DNA Polymerase
Stomach Neoplasms
Tumors
Mutation
Neoplasms
Mutagenesis
Amino Acid Substitution
Ports and harbors
Stomach
Carcinogenesis
Substitution reactions
Genes
Tissue
Phenotype
Amino Acids
Enzymes
Growth

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Donigan, Katherine A. ; Hile, Suzanne E. ; Eckert, Kristin ; Sweasy, Joann B. / The human gastric cancer-associated DNA polymerase β variant D160N is a mutator that induces cellular transformation. In: DNA Repair. 2012 ; Vol. 11, No. 4. pp. 381-390.
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The human gastric cancer-associated DNA polymerase β variant D160N is a mutator that induces cellular transformation. / Donigan, Katherine A.; Hile, Suzanne E.; Eckert, Kristin; Sweasy, Joann B.

In: DNA Repair, Vol. 11, No. 4, 01.04.2012, p. 381-390.

Research output: Contribution to journalArticle

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