PT - JOURNAL ARTICLE AU - Maria A. Andrianova AU - Georgii A. Bazykin AU - Sergey I. Nikolaev AU - Vladimir B. Seplyarskiy TI - Human mismatch repair system corrects errors produced during lagging strand replication more effectively AID - 10.1101/045278 DP - 2016 Jan 01 TA - bioRxiv PG - 045278 4099 - http://biorxiv.org/content/early/2016/03/23/045278.short 4100 - http://biorxiv.org/content/early/2016/03/23/045278.full AB - Mismatch repair (MMR) is one of the main systems maintaining fidelity of replication. Different effectiveness in correction of errors produced during replication of the leading and the lagging DNA strands was reported in yeast, but this effect is poorly studied in humans. Here, we use MMR-deficient (MSI) and MMR-proficient (MSS) cancer samples to investigate properties of the human MMR. MSI, but not MSS, cancers demonstrate unequal mutation rates between the leading and the lagging strands. The direction of strand asymmetry in MSI cancers matches that observed in cancers with mutated exonuclease domain of polymerase δ, indicating that polymerase δ contributes more mutations than its leading-strand counterpart, polymerase ε. As polymerase δ primarily synthesizes DNA during the lagging strand replication, this implies that mutations produced in wild type cells during lagging strand replication are repaired by the MMR ~3 times more effectively, compared to those produced on the leading strand.