Human DNA polymerase α interacts with mismatch repair proteins MSH 2 and MSH 6

High fidelity of genome duplication is ensured by cooperation of polymerase proofreading and mismatch repair (MMR) activities. Here, we show that human mismatch recognizing proteins MutS homolog 2 ( MSH 2) and MSH 6 copurify and interact with replicative Pol α. This enzyme also is the replicative primase and replicates DNA with poor fidelity. We show that MSH 2 associates with known human replication origins with different dynamics than DNA polymerase (Pol α). Furthermore, we explored the potential functional role of Pol α in the mismatch repair reaction using an in vitro mismatch repair assay and observed that Pol α promotes mismatch repair. Taken together, we show that human Pol α interacts with MSH 2‐ MSH 6 complex and propose that this interaction occurs during the mismatch repair reaction.