| First Author | Liu S | Year | 2015 |
| Journal | EMBO J | Volume | 34 |
| Issue | 13 | Pages | 1829-43 |
| PubMed ID | 25921062 | Mgi Jnum | J:222783 |
| Mgi Id | MGI:5645598 | Doi | 10.15252/embj.201489865 |
| Citation | Liu S, et al. (2015) Okazaki fragment maturation involves alpha-segment error editing by the mammalian FEN1/MutSalpha functional complex. EMBO J 34(13):1829-43 |
| abstractText | During nuclear DNA replication, proofreading-deficient DNA polymerase alpha (Pol alpha) initiates Okazaki fragment synthesis with lower fidelity than bulk replication by proofreading-proficient Pol delta or Pol epsilon. Here, we provide evidence that the exonuclease activity of mammalian flap endonuclease (FEN1) excises Pol alpha replication errors in a MutSalpha-dependent, MutLalpha-independent mismatch repair process we call Pol alpha-segment error editing (AEE). We show that MSH2 interacts with FEN1 and facilitates its nuclease activity to remove mismatches near the 5' ends of DNA substrates. Mouse cells and mice encoding FEN1 mutations display AEE deficiency, a strong mutator phenotype, enhanced cellular transformation, and increased cancer susceptibility. The results identify a novel role for FEN1 in a specialized mismatch repair pathway and a new cancer etiological mechanism. |
