Alaska Native People: Diet, Westernization and Health

Prior to westernization, the Alaska Native diet was one that included high omega-3 fatty acids and proteins and low in saturated fats and cholesterol. This may or may not provide protection against certain diseases. As westernization continues to changes the diet with each new generation, it is of great interest as to how it affects Alaska Native health. Alaska Native health has declined substantially within the last decade, and seems to continuously decline at an alarming rate. Investigating both the changing diet and the effects on Alaska Native health may provide a possible cause for this increasing health problem

Human DNA polymerase β polymorphism, Arg137Gln, impairs its polymerase activity and interaction with PCNA and the cellular base excision repair capacity

DNA polymerase β (Pol β) is a key enzyme in DNA base excision repair, and an important factor for maintaining genome integrity and stability. More than 30% of human tumors characterized to date express DNA Pol β variants, many of which result from a single nucleotide residue substitution. However, in most cases, their precise functional deficiency and relationship to cancer susceptibility are still unknown. In the current work, we show that a polymorphism encoding an arginine to glutamine substitution, R137Q, has lower polymerase activity. The substitution also affects the interaction between Pol β and proliferating cell nuclear antigen (PCNA). These defects impair the DNA repair capacity of Pol β in reconstitution assays, as well as in cellular extracts. Expression of wild-type Pol β in pol β−/− mouse embryonic fibroblast (MEF) cells restored cellular resistance to DNA damaging reagents such as methyl methanesulfonate (MMS) and N-methyl-N-nitrosourea (MNU), while expression of R137Q in pol β−/− MEF cells failed to do so. These data indicate that polymorphisms in base excision repair genes may contribute to the onset and development of cancers