TY - JOUR
T1 - The human gastric cancer-associated DNA polymerase β variant D160N is a mutator that induces cellular transformation
AU - Donigan, Katherine A.
AU - Hile, Suzanne E.
AU - Eckert, Kristin A.
AU - Sweasy, Joann B.
N1 - Funding Information:
This work was supported by grants from the NIH Predoctoral Genetics Training Grant T32 GM007499 to K.A.D. and P01CA129186 to J.B.S. We thank members of the Sweasy lab, including D. Murphy, A. Nemec and S. Dalal, for insightful discussions regarding this work and G. Sun for technical assistance.
PY - 2012/4/1
Y1 - 2012/4/1
N2 - 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.
AB - 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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U2 - 10.1016/j.dnarep.2012.01.004
DO - 10.1016/j.dnarep.2012.01.004
M3 - Article
C2 - 22341651
AN - SCOPUS:84859006366
SN - 1568-7864
VL - 11
SP - 381
EP - 390
JO - DNA Repair
JF - DNA Repair
IS - 4
ER -
