We also studied the effect of strong nucleosomes on replication fidelity by examining data from children with inherited biallelic MMR deficiency (bMMRD)41; these include ultrahypermutated genomes arising from Pol ε and polymerase δ defects (Pol δ, the major replicase for the lagging strand; POLD1 encodes the catalytic subunit of Pol δ). Here, POLD1 is linked to mismatch repair cancer syndrome 1.