In all, TLS components are dispensable in the somatic lineages but essential in the germline. PGCs lacking TLS factors fail to express germline genes or perform global DNA demethylation showing a developmental block, explaining infertility of TLS-deficient organisms
 8/9

Molecular characterisation of mutant day 12.5 PGCs shows a failure of global DNA demethylation. The level of methylation is more similar to epiblast cells than PGCs. The germline transcriptional programme is also corrupted with mutant PGCs failing to engage germline genes 7/9

In the absence of REV1 and upon mutation of PCNA K164, PGCs display higher burdens of DNA damage, perturbed cell cycle dynamics and reduced proliferation 6/9

However, PCNA K164 modification is dispensable for maintaining all somatic lineages studied revealing a striking dichotomy between the germline and soma 5/9

This defect is due to role of REV1 in translesion synthesis (TLS) as we find that PCNA K164 and REV7 are also required in PGCs. The timing, magnitude of PGC loss and phenotype of remaining PGCs of TLS mutants are indistinguishable. 4/9

This requirement is conserved to mice where REV1 is essential for fertility due to a role in embryonic germ cell development. 3/9

We find that REV1, a DNA repair factor implicated in human infertility, is required for the induction of human PGC-like cells. In the absence of REV1, there is an almost complete failure of hPGCLC induction 2/9