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Acetylation of Dna2 and Fen1 by P300 Promotes Long Flaps Favoring DNA Stability
Author(s) -
Balakrishnan Lata,
Stewart Jason A,
Polaczek Piotr,
Campbell Judith L,
Bambara Robert A
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.492.1
Subject(s) - helicase , nuclease , dna , dna repair , microbiology and biotechnology , okazaki fragments , chromatin , dna replication , nucleotide excision repair , biology , chemistry , biochemistry , eukaryotic dna replication , gene , rna
Flap endonuclease 1 (FEN1) and Dna2 endonuclease/helicase (Dna2) sequentially coordinate their nuclease activities for efficient resolution of flap structures that are created during the maturation of Okazaki fragments and repair of DNA damage. FEN1 can be post‐translationally modified by the transcriptional coactivator, p300. Acetylation of FEN1 by p300 inhibits its endonuclease activity impairing flap cleavage, a seemingly undesirable effect. We now show that p300 also acetylates Dna2. However, in contrast to FEN1, acetylation of Dna2 stimulates its 5′–3′ endonuclease, the 5′–3′ helicase and DNA‐dependent ATPase activities, allowing more efficient processing of long flaps. Furthermore, acetylated Dna2 binds its DNA substrates with higher affinity. Dna2 and FEN1 form a complex with p300 both in vitro and in vivo. Differential regulation of the activities of the two endonucleases by p300 indicates a mechanism in which the acetylase promotes formation of longer flaps in the cell at the same time as insuring correct processing. Such intentional formation of longer flaps mediated by p300 in an active chromatin environment would increase the re‐synthesis patch size, providing increased opportunity for incorrect nucleotide removal during DNA replication and damaged nucleotide removal during DNA repair. This work was funded by the National Institute of Health grant GM024441 to R.A.B.