Significance Fork regression is a way of circumventing or dealing with DNA lesions and is important to genome integrity. Fork regression is performed by double-strand DNA ATPases that initially cause newly synthesized strands to unpair from the parental strands, followed by pairing of the new strands and reversal of the fork. This study shows that Mcm10, an essential replication factor, efficiently anneals complementary strands and also inhibits fork regression by SMARCAL1. Moreover, the study localizes the Mcm10 DNA-binding domain to the N-terminal domains of the replicative CMG helicase at the forked nexus. Thus, forks that are unimpeded would contain Mcm10 at a strategic position where its DNA-binding and/or annealing function may block fork regression enzymes and thereby protect active forks from becoming reversed.