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

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

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

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

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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