We have identified a unique signature for DNA polymerase zeta which is to generate tandem mutations druing somatic hypermutation. Using mice deficient for various polymerases, we observed that polymerase eta is a dominant protein, and the effect of polymerase zeta was more pronounced in the absence of polymerase eta. Furthermore, data sugest that polymerase zeta functions in the MSH2-MSH6 pathway. An advantage to using polymerase zeta to inroduce tandem mutations would be to efficiently change amino acids in variable genes to generate higher affinity antibodies.

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National Institute on Aging
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Zanotti, Kimberly J; Gearhart, Patricia J (2016) Antibody diversification caused by disrupted mismatch repair and promiscuous DNA polymerases. DNA Repair (Amst) 38:110-6
Maul, Robert W; MacCarthy, Thomas; Frank, Ekaterina G et al. (2016) DNA polymerase ? functions in the generation of tandem mutations during somatic hypermutation of antibody genes. J Exp Med 213:1675-83
Zanotti, Kimberly J; Maul, Robert W; Castiblanco, Diana P et al. (2015) ATAD5 deficiency decreases B cell division and Igh recombination. J Immunol 194:35-42
Maul, Robert W; Gearhart, Patricia J (2014) Refining the Neuberger model: Uracil processing by activated B cells. Eur J Immunol 44:1913-6
Saribasak, Huseyin; Maul, Robert W; Cao, Zheng et al. (2012) DNA polymerase ? generates tandem mutations in immunoglobulin variable regions. J Exp Med 209:1075-81
Pape, Kathryn A; Taylor, Justin J; Maul, Robert W et al. (2011) Different B cell populations mediate early and late memory during an endogenous immune response. Science 331:1203-7
Maul, Robert W; Gearhart, Patricia J (2010) AID and somatic hypermutation. Adv Immunol 105:159-91
Maul, Robert W; Gearhart, Patricia J (2010) Controlling somatic hypermutation in immunoglobulin variable and switch regions. Immunol Res 47:113-22
Gearhart, Patricia J; Lindahl, Tomas; Neuberger, Michael S (2009) Preface. Philos Trans R Soc Lond B Biol Sci 364:561-2
Saribasak, Huseyin; Rajagopal, Deepa; Maul, Robert W et al. (2009) Hijacked DNA repair proteins and unchained DNA polymerases. Philos Trans R Soc Lond B Biol Sci 364:605-11