Reactome | Removal of remaining Flap from the C-strand

Removal of remaining Flap from the C-strand

Stable Identifier

R-HSA-174446

Type

Reaction [transition]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

Locations in the PathwayBrowser

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Cell Cycle (Homo sapiens)

- Chromosome Maintenance (Homo sapiens)
  - Telomere Maintenance (Homo sapiens)
    - Extension of Telomeres (Homo sapiens)
      - Telomere C-strand (Lagging Strand) Synthesis (Homo sapiens)
        
        Processive synthesis on the C-strand of the telomere (Homo sapiens)
        
        Removal of the Flap Intermediate from the C-strand (Homo sapiens)
        
        Removal of remaining Flap from the C-strand (Homo sapiens)

General

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Removal of remaining Flap from the C-strand

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The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

The remaining flap, which is too short to support RPA binding, is then processed by FEN1. There is evidence that binding of RPA to the displaced end of the RNA-containing Okazaki fragment prevents FEN1 from accessing the substrate. FEN1 is a structure-specific endonuclease that cleaves near the base of the flap at a position one nucleotide into the annealed region. Biochemical studies have shown that the preferred substrate for FEN1 consists of a one-nucleotide 3'-tail on the upstream primer in addition to the 5'-flap of the downstream primer (Harrington and Lieber 1994, Harrington and Lieber 1995, Murante et al. 1996, Lieber 1997, Kaiser et al. 1999, Xu et al. 2000, Kao et al. 2002). The interaction of FEN1 with WRN, a RECQ family DNA helicase, is needed for successful flap cleavage during telomeric strand displacement synthesis (Saharia et al. 2010, Li et al. 2017).

Literature References

PubMed ID	Title	Journal	Year
20551483	FEN1 ensures telomere stability by facilitating replication fork re-initiation Saharia, A, Teasley, DC, Duxin, JP, Dao, B, Chiappinelli, KB, Stewart, SA	J. Biol. Chem.	2010
27849570	The Werner Syndrome Helicase Coordinates Sequential Strand Displacement and FEN1-Mediated Flap Cleavage during Polymerase δ Elongation Li, B, Reddy, S, Comai, L	Mol. Cell. Biol.	2017