RAD27/YKL113C Summary Help

Standard Name RAD27 1
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, for long-patch base-excision repair and large loop repair (LLR), ribonucleotide excision repair; member of the S. pombe RAD2/FEN1 family; relocalizes to the cytosol in response to hypoxia (4, 5, 6, 7, 8 and see Summary Paragraph)
Name Description RADiation sensitive 1
Chromosomal Location
ChrXI:225875 to 224727 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Gbrowse
Gene Ontology 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
High-throughput
Regulators 2 genes
Resources
Classical genetics
null
reduction of function
Large-scale survey
null
Resources
949 total interaction(s) for 372 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 8
  • Affinity Capture-RNA: 1
  • Affinity Capture-Western: 7
  • Reconstituted Complex: 5
  • Two-hybrid: 3

Genetic Interactions
  • Dosage Growth Defect: 2
  • Dosage Lethality: 2
  • Dosage Rescue: 11
  • Negative Genetic: 331
  • Phenotypic Enhancement: 44
  • Phenotypic Suppression: 5
  • Positive Genetic: 27
  • Synthetic Growth Defect: 223
  • Synthetic Lethality: 273
  • Synthetic Rescue: 7

Resources
Expression Summary
histogram
Resources
Length (a.a.) 382
Molecular Weight (Da) 43,279
Isoelectric Point (pI) 9.51
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrXI:225875 to 224727 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
SGD ORF map
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..1149 225875..224727 2011-02-03 1996-07-31
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
Resources
External Links All Associated Seq | E.C. | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000001596
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 9). 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, 10, 11). 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 (12, 9). RAD27 has also been implicated in double-strand break repair via non-homologous end-joining (13).

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, 14). 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 (15, 16, 17). RAD27 expression is cell-cyle regulated (1).

Rad27p is highly conserved in bacteria, other fungi, and mammals (18, 1, 19, 14). It contains three highly conserved domains, two of which are conserved in prokaryotes (20). 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 (21, 15, 22, 23, 24, 25, 26).

Last updated: 2007-10-05 Contact SGD

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) Sommer D, et al.  (2008) Partial reconstitution of DNA large loop repair with purified proteins from Saccharomyces cerevisiae. Nucleic Acids Res 36(14):4699-707
7) Sparks JL, et al.  (2012) RNase H2-initiated ribonucleotide excision repair. Mol Cell 47(6):980-6
8) Ghosh Dastidar R, et al.  (2012) The nuclear localization of SWI/SNF proteins is subjected to oxygen regulation. Cell Biosci 2(1):30
9) Liu Y, et al.  (2004) Flap endonuclease 1: a central component of DNA metabolism. Annu Rev Biochem 73:589-615
10) Rossi ML and Bambara RA  (2006) Reconstituted Okazaki fragment processing indicates two pathways of primer removal. J Biol Chem 281(36):26051-61
11) 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
12) 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
13) 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
14) 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
15) 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
16) Symington LS  (1998) Homologous recombination is required for the viability of rad27 mutants. Nucleic Acids Res 26(24):5589-95
17) 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
18) 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
19) 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
20) Lieber MR  (1997) The FEN-1 family of structure-specific nucleases in eukaryotic DNA replication, recombination and repair. Bioessays 19(3):233-40
21) 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
22) 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
23) 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
24) Otto C, 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
25) 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
26) 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