DNA replication is a very precisely regulated mechanism which ensures the accurate genome duplication before cell division. However, different exogenous or endogenous factors may impede DNA replication progression leading to DNA replication stress (DRS). In response to DRS, replication forks stall and may eventually collapse. Cells have developed various repair pathways in order to cope with stalled and collapsed forks. Break-induced replication repair (BIR), is a major pathway responsible for repair of collapsed replication forks. POLD3 is one of the subunits of POLδ complex known to have a role both in normal replication and BIR. In this study, we intended to identify which domain of POLD3 is important for normal replication and which has a role in BIR. After depleting cells' endogenous POLD3, we managed to rescue normal replication via transfecting cells with exogenous POLD3. Furthermore, preliminary data indicate that the C-terminal part of POLD3 is required for efficient response to DNA damage. This study provides the essential tools for further investigation of POLD3's role in BIR.