The characterization of a mammalian DNA structure-specific endonuclease - PubMed (original) (raw)
The characterization of a mammalian DNA structure-specific endonuclease
J J Harrington et al. EMBO J. 1994.
Abstract
The repair of some types of DNA double-strand breaks is thought to proceed through DNA flap structure intermediates. A DNA flap is a bifurcated structure composed of double-stranded DNA and a displaced single-strand. To identify DNA flap cleaving activities in mammalian nuclear extracts, we created an assay utilizing a synthetic DNA flap substrate. This assay has allowed the first purification of a mammalian DNA structure-specific nuclease. The enzyme described here, flap endonuclease-1 (FEN-1), cleaves DNA flap strands that terminate with a 5' single-stranded end. As expected for an enzyme which functions in double-strand break repair flap resolution, FEN-1 cleavage is flap strand-specific and independent of flap strand length. Furthermore, efficient flap cleavage requires the presence of the entire flap structure. Substrates missing one strand are not cleaved by FEN-1. Other branch structures, including Holliday junctions, are also not cleaved by FEN-1. In addition to endonuclease activity, FEN-1 has a 5'-3' exonuclease activity which is specific for double-stranded DNA. The endo- and exonuclease activities of FEN-1 are discussed in the context of DNA replication, recombination and repair.
Similar articles
- DNA structural elements required for FEN-1 binding.
Harrington JJ, Lieber MR. Harrington JJ, et al. J Biol Chem. 1995 Mar 3;270(9):4503-8. doi: 10.1074/jbc.270.9.4503. J Biol Chem. 1995. PMID: 7876218 - Double-strand DNA break formation mediated by flap endonuclease-1.
Vispé S, Ho EL, Yung TM, Satoh MS. Vispé S, et al. J Biol Chem. 2003 Sep 12;278(37):35279-85. doi: 10.1074/jbc.M303448200. Epub 2003 Jun 27. J Biol Chem. 2003. PMID: 12832398 - Processing of branched DNA intermediates by a complex of human FEN-1 and PCNA.
Wu X, Li J, Li X, Hsieh CL, Burgers PM, Lieber MR. Wu X, et al. Nucleic Acids Res. 1996 Jun 1;24(11):2036-43. doi: 10.1093/nar/24.11.2036. Nucleic Acids Res. 1996. PMID: 8668533 Free PMC article. - The wonders of flap endonucleases: structure, function, mechanism and regulation.
Finger LD, Atack JM, Tsutakawa S, Classen S, Tainer J, Grasby J, Shen B. Finger LD, et al. Subcell Biochem. 2012;62:301-26. doi: 10.1007/978-94-007-4572-8_16. Subcell Biochem. 2012. PMID: 22918592 Free PMC article. Review. - Substrate recognition and catalysis by flap endonucleases and related enzymes.
Tomlinson CG, Atack JM, Chapados B, Tainer JA, Grasby JA. Tomlinson CG, et al. Biochem Soc Trans. 2010 Apr;38(2):433-7. doi: 10.1042/BST0380433. Biochem Soc Trans. 2010. PMID: 20298197 Review.
Cited by
- Does the XPA-FEN1 Interaction Concern to Nucleotide Excision Repair or Beyond?
Krasikova YS, Maltseva EA, Khodyreva SN, Evdokimov AN, Rechkunova NI, Lavrik OI. Krasikova YS, et al. Biomolecules. 2024 Jul 9;14(7):814. doi: 10.3390/biom14070814. Biomolecules. 2024. PMID: 39062528 Free PMC article. - FEN1 Inhibition as a Potential Novel Targeted Therapy against Breast Cancer and the Prognostic Relevance of FEN1.
Berfelde J, Hildebrand LS, Kuhlmann L, Fietkau R, Distel LV. Berfelde J, et al. Int J Mol Sci. 2024 Feb 9;25(4):2110. doi: 10.3390/ijms25042110. Int J Mol Sci. 2024. PMID: 38396787 Free PMC article. - DNA combing versus DNA spreading and the separation of sister chromatids.
Meroni A, Wells SE, Fonseca C, Ray Chaudhuri A, Caldecott KW, Vindigni A. Meroni A, et al. J Cell Biol. 2024 Apr 1;223(4):e202305082. doi: 10.1083/jcb.202305082. Epub 2024 Feb 5. J Cell Biol. 2024. PMID: 38315097 Free PMC article. - Antioxidant enzyme and DNA base repair genetic risk scores' associations with systemic oxidative stress biomarker in pooled cross-sectional studies.
Mao Z, Gray ALH, Thyagarajan B, Bostick RM. Mao Z, et al. Front Aging. 2023 Apr 21;4:1000166. doi: 10.3389/fragi.2023.1000166. eCollection 2023. Front Aging. 2023. PMID: 37152862 Free PMC article. - Bacillus subtilis encodes a discrete flap endonuclease that cleaves RNA-DNA hybrids.
Lowder FC, Simmons LA. Lowder FC, et al. PLoS Genet. 2023 May 5;19(5):e1010585. doi: 10.1371/journal.pgen.1010585. eCollection 2023 May. PLoS Genet. 2023. PMID: 37146086 Free PMC article.
References
- Mol Cell Biol. 1986 Dec;6(12):4295-304 - PubMed
- Cell. 1986 Sep 26;46(7):963-72 - PubMed
- Cell. 1988 Aug 12;54(4):453-60 - PubMed
- EMBO J. 1988 May;7(5):1527-35 - PubMed
- Cell. 1988 Oct 7;55(1):7-16 - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Research Materials
Miscellaneous