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

DNA Repair
Katherine A DoniganJoann B Sweasy

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.

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Citations

May 11, 2012·The Journal of Biological Chemistry·Antonia A NemecJoann B Sweasy
Dec 1, 2012·Mutation Research·Ashley B SjolundJoann B Sweasy
Feb 13, 2014·Journal of the American Chemical Society·Dumitru ArianMarc M Greenberg
Jun 12, 2013·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Min LiGuoqiang Zhao
May 2, 2014·DNA Repair·Susan S Wallace

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