single cell analysis of Rev3L deficient mutant genome pre-tumor stage and the post-tumor stage.

Rev3l is a catalytic subunit of TLS polymerase Pol-zeta. TLS polymerase is responsible for induction of point mutation at sites of DNA damage. Consistent with this, a reduction in the induced mutation frequency in rev3l-deficient cells has been reported several organisms. We established rev3l knockout mutants in the small laboratory fish Medaka. While in mice rev3l deficiency leads to embryonic lethality, homozygous rev3l -/- medaka were viable through adulthood. However, the mutant fish showed reduced lifespan. All mutant fish died from intestinal tumors by the age 9 months. To investigate the cause of the high incidence of intestinal tumor in rev3l -/- mutant, genome of the mutant was examined at pre-tumor stage (cultured cells derived from embryo) and the post-tumor stage (cells disseminated into abdomen of tumor-bearing fish).