A new class of errant DNA polymerases provides candidates for somatic hypermutation

The mechanism of somatic hypermutation of the immunoglobulin genes remains a mystery after nearly 30 years of intensive research in the field. While m any clues to the process have been discovered in terms of the genetic eleme nts required in the immunoglobulin genes, the key enzymatic players that me diate the introduction of mutations into the variable region are unknown. T he recent wave of newly discovered eukaryotic DNA polymerases have given a fresh supply of potential candidates and a renewed vigour in the search for the elusive mutator factor governing affinity maturation. In this paper, w e discuss the relevant genetic and biochemical evidence known to dale regar ding both somatic hypermutation and the new DNA polymerases and address how the two fields can be brought together to identify the strongest candidate s for further study. In particular we discuss evidence for the in vitro bio chemical misincorporation properties of human Rad30B/ Pol iota and how it c ompares to the in vivo somatic hypermutation spectra.