RAD27/YKL113C Summary 
RAD27 BASIC INFORMATION
| Standard Name | RAD27 1 |
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| Systematic Name | YKL113C |
| Alias | ERC11 , RTH1 2 , FEN1 3 |
| Feature Type | ORF, Verified |
| Description | 5' to 3' exonuclease, 5' flap endonuclease, required for Okazaki fragment processing and maturation as well as for long-patch base-excision repair; member of the S. pombe RAD2/FEN1 family (4, 5 and see Summary Paragraph) 
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| Name Description | RADiation sensitive 1 |
| GO Annotations | All RAD27 GO evidence and references |
|---|---|
| View Computational GO annotations for RAD27 | |
| Molecular Function | |
| Manually curated | |
| Biological Process | |
| Manually curated | |
| Cellular Component | |
| Manually curated |
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| High-throughput |
| Interactions | RAD27 All interactions details and references |
|---|---|
| 585 total interaction(s) for 252 unique genes/features. | |
| Physical Interactions |
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| Genetic Interactions |
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| External Links | All Associated Seq | Entrez Gene | Entrez RefSeq Protein | MIPS | UniProtKB |
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| Primary SGDID | S000001596 |
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RAD27 RESOURCES
| SGD ORF map | GBrowse |
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Click on histogram for expression summary
Expression Summary
ADDITIONAL INFORMATION for RAD27
SUMMARY PARAGRAPH for RAD27
RAD27 encodes a multi-functional nuclease involved in processing Okazaki fragments during DNA replication, base excision repair (BER), and maintaining genome stability (reviewed in 6). Its 5'-flap endonuclease activity is required to cleave the 5' flap from Okazaki fragments that is generated during lagging strand synthesis and to remove the 5'-deoxyribosephosphate end that is formed at apurinic/apyrimidinic sites during BER (4, 7, 8). A double-flap structure with a 1-nt 3' tail has been proposed as the optimal substrate for its endonucleolytic activity (4). The 5' to 3' exonuclease of Rad27p is involved in preventing the expansion of di- and trinucleotide repeats by removing secondary structures that are formed by the repeated sequences (9, 6). RAD27 has also been implicated in double-strand break repair via non-homologous end-joining (10).
Despite its role in many aspects of DNA metabolism, rad27 null mutants are viable but grow slowly (1, 2). rad27 null mutants are sensitive to UV radiation and methylmethane sulfonate (MMS) but not ionizing radiation, consistent with its role in processing intermediates that are formed during BER (1, 11). rad27 mutants confer an increased rate of recombination and are synthetically lethal with mutations in genes involved in homologous recombination, suggesting that 5' flaps can be removed via homologous recombination (12, 13, 14). RAD27 expression is cell-cyle regulated (1).
Rad27p is highly conserved in bacteria, other fungi, and mammals (15, 1, 16, 11). It contains three highly conserved domains, two of which are conserved in prokaryotes (17). Because deletion of RAD27 in S. cerevisiae leads to expansion of repetitive DNA and trinucleotide repeat instability, RAD27 (known as FEN1 in mammals and humans) has been implicated in the triplet repeat expansions that lead to Huntington disease and fragile X (18, 12, 19, 20, 21, 22, 23).
Last updated: 2007-10-05
REFERENCES CITED ON THIS PAGE [View Complete Literature Guide for RAD27]
| 1) | Reagan MS, et al. (1995) Characterization of a mutant strain of Saccharomyces cerevisiae with a deletion of the RAD27 gene, a structural homolog of the RAD2 nucleotide excision repair gene. J Bacteriol 177(2):364-71 |
| 2) | Sommers CH, et al. (1995) Conditional lethality of null mutations in RTH1 that encodes the yeast counterpart of a mammalian 5'- to 3'-exonuclease required for lagging strand DNA synthesis in reconstituted systems. J Biol Chem 270(9):4193-6 |
| 3) | Gary R, et al. (1999) A novel role in DNA metabolism for the binding of Fen1/Rad27 to PCNA and implications for genetic risk. Mol Cell Biol 19(8):5373-82 |
| 4) | Kao HI, et al. (2002) Cleavage specificity of Saccharomyces cerevisiae flap endonuclease 1 suggests a double-flap structure as the cellular substrate. J Biol Chem 277(17):14379-89 |
| 5) | Ayyagari R, et al. (2003) Okazaki fragment maturation in yeast. I. Distribution of functions between FEN1 AND DNA2. J Biol Chem 278(3):1618-25 |
| 6) | Liu Y, et al. (2004) Flap endonuclease 1: a central component of DNA metabolism. Annu Rev Biochem 73:589-615 |
| 7) | Rossi ML and Bambara RA (2006) Reconstituted Okazaki fragment processing indicates two pathways of primer removal. J Biol Chem 281(36):26051-61 |
| 8) | Wu X and Wang Z (1999) Relationships between yeast Rad27 and Apn1 in response to apurinic/apyrimidinic (AP) sites in DNA. Nucleic Acids Res 27(4):956-62 |
| 9) | Xie Y, et al. (2001) Identification of rad27 mutations that confer differential defects in mutation avoidance, repeat tract instability, and flap cleavage. Mol Cell Biol 21(15):4889-99 |
| 10) | Tseng HM and Tomkinson AE (2004) Processing and joining of DNA ends coordinated by interactions among Dnl4/Lif1, Pol4, and FEN-1. J Biol Chem 279(46):47580-8 |
| 11) | Hansen RJ, et al. (2000) Sensitivity of a S. cerevisiae RAD27 deletion mutant to DNA-damaging agents and in vivo complementation by the human FEN-1 gene. Mutat Res 461(3):243-8 |
| 12) | Tishkoff DX, et al. (1997) A novel mutation avoidance mechanism dependent on S. cerevisiae RAD27 is distinct from DNA mismatch repair. Cell 88(2):253-63 |
| 13) | Symington LS (1998) Homologous recombination is required for the viability of rad27 mutants. Nucleic Acids Res 26(24):5589-95 |
| 14) | Debrauwere H, et al. (2001) Links between replication and recombination in Saccharomyces cerevisiae: a hypersensitive requirement for homologous recombination in the absence of Rad27 activity. Proc Natl Acad Sci U S A 98(15):8263-9 |
| 15) | Carr AM, et al. (1993) Evolutionary conservation of excision repair in Schizosaccharomyces pombe: evidence for a family of sequences related to the Saccharomyces cerevisiae RAD2 gene. Nucleic Acids Res 21(6):1345-9 |
| 16) | Bibikova M, et al. (1998) Characterization of FEN-1 from Xenopus laevis. cDNA cloning and role in DNA metabolism. J Biol Chem 273(51):34222-9 |
| 17) | Lieber MR (1997) The FEN-1 family of structure-specific nucleases in eukaryotic DNA replication, recombination and repair. Bioessays 19(3):233-40 |
| 18) | Johnson RE, et al. (1995) Requirement of the yeast RTH1 5' to 3' exonuclease for the stability of simple repetitive DNA. Science 269(5221):238-40 |
| 19) | Kokoska RJ, et al. (1998) Destabilization of yeast micro- and minisatellite DNA sequences by mutations affecting a nuclease involved in Okazaki fragment processing (rad27) and DNA polymerase delta (pol3-t). Mol Cell Biol 18(5):2779-88 |
| 20) | White PJ, et al. (1999) Stability of the human fragile X (CGG)(n) triplet repeat array in Saccharomyces cerevisiae deficient in aspects of DNA metabolism. Mol Cell Biol 19(8):5675-84 |
| 21) | Otto CJ, et al. (2001) The "flap" endonuclease gene FEN1 is excluded as a candidate gene implicated in the CAG repeat expansion underlying Huntington disease. Clin Genet 59(2):122-7 |
| 22) | Singh P, et al. (2007) Concerted action of exonuclease and Gap-dependent endonuclease activities of FEN-1 contributes to the resolution of triplet repeat sequences (CTG)n- and (GAA)n-derived secondary structures formed during maturation of Okazaki fragments. J Biol Chem 282(6):3465-77 |
| 23) | Yang J and Freudenreich CH (2007) Haploinsufficiency of yeast FEN1 causes instability of expanded CAG/CTG tracts in a length-dependent manner. Gene 393(1-2):110-5 |
