The access to DNA within nucleosomes is greatly restricted for most enzymes
and trans-acting factors that bind DNA. We report here that human DNA liga
se I, which carries out the final step of Okazaki fragment processing and o
f many DNA repair pathways, can access DNA that is wrapped about the surfac
e of a nucleosome in vitro and carry out its enzymatic function with high e
fficiency. In addition, we find that ligase activity is not affected by the
binding of linker histone (H1) but is greatly influenced by the dispositio
n of the core histone tail domains. These results suggest that the window o
f opportunity for human DNA ligase I may extend well beyond the first stage
s of chromatin reassembly after DNA replication or repair.