(H) Our current working model depicting HMCES mechanism of action on replication fork. Upon encountering oxidative base damage on replication fork, HMCES along with BER machinery can successfully remove modified base to resume replication. This mechanism would result in error-free replication and maintain genomic integrity between parental and nascent replication forks. In the absence of HMCES, however, the replication fork can proceed only by replicating through the damage, often by misrecognition and misincorporation of bases by replicative or translesion polymerases, leading to replication errors. HRR factors such as CtIP, BRCA2, BRCA1 and PALB2 are indispensable for processing the damage, possible recruitment of TLS polymerase, and replication fork restart. 