Human DNA polymerase η promotes DNA synthesis from strand invasion intermediates of homologous recombination

Stalled replication forks pose a serious threat to genome integrity. To overcome the catastrophic consequences associated with fork demise, translesion synthesis (TLS) polymerases such as pol eta promote DNA synthesis past lesions. Alternatively, a stalled fork may collapse and undergo repair by homologous recombination. By using fractionated cell extracts and purified recombinant proteins, we show that pol eta extends DNA synthesis from D loop recombination intermediates in which an invading strand serves as the primer. Extracts from XP-V cells, which are defective in pol eta, exhibit severely reduced D loop extension activity. The D loop extension activity of pol eta is unusual, as this reaction cannot be promoted by the replicative DNA polymerase alpha or by other TLS polymerases such as pol iota. Moreover, we find that pol eta interacts with RAD51 recombinase and RAD51 stimulates pol eta-mediated D loop extension. Our results indicate a dual function for pol eta at stalled replication forks: the promotion of translesion synthesis and the reinitiation of DNA synthesis by homologous recombination repair.