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Acetylation of Dna2 Endonuclease/Helicase and Flap Endonuclease 1 by p300 Promotes DNA Stability by Creating Long Flap Intermediates

fanzhiqiang 添加于 2010-3-26 10:19 | 2391 次阅读 | 0 个评论

作者
Balakrishnan L, Stewart J, Polaczek P, Campbell JL, Bambara RA
摘要
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. Acetylation of FEN1 by p300 inhibits its endonuclease activity, impairing flap cleavage, a seemingly undesirable effect. We now show that p300 also acetylates Dna2, stimulating its 5'-3' endonuclease, the 5'-3' helicase, and DNA-dependent ATPase activities. Furthermore, acetylated Dna2 binds its DNA substrates with higher affinity. 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 ensuring correct processing. Intentional formation of longer flaps mediated by p300 in an active chromatin environment would increase the resynthesis patch size, providing increased opportunity for incorrect nucleotide removal during DNA replication and damaged nucleotide removal during DNA repair. For example, altering the ratio between short and long flap Okazaki fragment processing would be a mechanism for better correction of the error-prone synthesis catalyzed by DNA polymerase alpha.
详细资料
- 关键词: TRANSCRIPTIONAL COACTIVATOR P300; OKAZAKI FRAGMENT MATURATION; BASE EXCISION-REPAIR; CELL NUCLEAR ANTIGEN; POLYMERASE-DELTA; REPLICATION FORK; HUMAN FEN1; YEAST; GLYCOSYLASE; CLEAVAGE
- 文献种类:期刊
- 期刊名称: JOURNAL OF BIOLOGICAL CHEMISTRY
- 期卷页: 2010年第285卷第7期 4398-4404页
- 出版社: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
- 地址: 1. Univ Rochester, Sch Med & Dent, Dept Biochem & Biophys, Rochester, NY 14642 USA 2. CALTECH, Braun Labs, Pasadena, CA 91125 USA
- ISBN: 0021-9258
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