TOP1/YOL006C Summary Help

Standard Name TOP1 1
Systematic Name YOL006C
Alias MAK1 , MAK17
Feature Type ORF, Verified
Description Topoisomerase I; nuclear enzyme that relieves torsional strain in DNA by cleaving and re-sealing the phosphodiester backbone; relaxes both positively and negatively supercoiled DNA; functions in replication, transcription, and recombination; role in processing ribonucleoside monophosphates in genomic DNA into irreversible single-strand breaks (1, 2, 3, 4 and see Summary Paragraph)
Name Description TOPoisomerase 1
Chromosomal Location
ChrXV:315387 to 313078 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Gbrowse
Genetic position: 3 cM
Gene Ontology Annotations All TOP1 GO evidence and references
  View Computational GO annotations for TOP1
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 1 genes
Resources
Classical genetics
null
Large-scale survey
null
overexpression
Resources
655 total interaction(s) for 443 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 45
  • Affinity Capture-RNA: 2
  • Affinity Capture-Western: 9
  • Biochemical Activity: 1
  • PCA: 1
  • Two-hybrid: 12

Genetic Interactions
  • Dosage Growth Defect: 1
  • Dosage Rescue: 2
  • Negative Genetic: 159
  • Phenotypic Enhancement: 16
  • Phenotypic Suppression: 13
  • Positive Genetic: 74
  • Synthetic Growth Defect: 274
  • Synthetic Lethality: 37
  • Synthetic Rescue: 9

Resources
Expression Summary
histogram
Resources
Length (a.a.) 769
Molecular Weight (Da) 89,995
Isoelectric Point (pI) 9.38
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrXV:315387 to 313078 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
SGD ORF map
Genetic position: 3 cM
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..2310 315387..313078 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 SGDIDS000005366
SUMMARY PARAGRAPH for TOP1

Topoisomerases catalyze the interconversion between topological states of DNA by breaking and rejoining DNA strands. These changes in DNA topology are required during several cellular processes such as replication, transcription, recombination, and chromosome condensation (5). There are three classes of topoisomerases that are distinguished by substrate (IA, IB, II). Type I topoisomerases cleave one DNA strand, while Type II enzymes cleave a pair of complementary DNA strands (6). The type IB topoisomerases relax both positively and negatively supercoiled DNA; TOP1 encodes the type IB enzyme in yeast (1, 7). Type IA topoisomerase, encoded by TOP3 in yeast, relaxes only negatively supercoiled DNA, and yeast topoisomerase II is encoded by the TOP2 gene (6).

Topoisomerases are highly conserved; yeast Top1p shares 57% identity with human Top1 (8). The Top1 protein, like other type IB topoisomerases, relaxes supercoiled DNA by forming a DNA-enzyme complex and transiently cleaving one strand via a nucleophilic attack that results in a covalent linkage with the 3' end of the cleaved strand. The 5' end can then rotate freely (5).

Top1p is the target of the antitumor drug camptothecin (9). Camptothecin increases the half-life of the enzyme-DNA complex, which results in double-stranded DNA breaks during DNA replication (10). Specific amino acid substitutions in Top1p have the same effect as the drug (11). Suppressors of these mutations were identified that reduced the enzyme's affinity for DNA (12).

Last updated: 1999-11-09 Contact SGD

References cited on this page View Complete Literature Guide for TOP1
1) Thrash C, et al.  (1985) Cloning, characterization, and sequence of the yeast DNA topoisomerase I gene. Proc Natl Acad Sci U S A 82(13):4374-8
2) Roca J  (1995) The mechanisms of DNA topoisomerases. Trends Biochem Sci 20(4):156-60
3) Woo MH, et al.  (2003) Locking the DNA topoisomerase I protein clamp inhibits DNA rotation and induces cell lethality. Proc Natl Acad Sci U S A 100(24):13767-72
4) Kim N, et al.  (2011) Mutagenic processing of ribonucleotides in DNA by yeast topoisomerase I. Science 332(6037):1561-4
5) Berger JM  (1998) Structure of DNA topoisomerases. Biochim Biophys Acta 1400(1-3):3-18
6) Wang JC  (1996) DNA topoisomerases. Annu Rev Biochem 65:635-92
7) Goto T and Wang JC  (1985) Cloning of yeast TOP1, the gene encoding DNA topoisomerase I, and construction of mutants defective in both DNA topoisomerase I and DNA topoisomerase II. Proc Natl Acad Sci U S A 82(21):7178-82
8) Mushegian AR, et al.  (1998) Large-scale taxonomic profiling of eukaryotic model organisms: a comparison of orthologous proteins encoded by the human, fly, nematode, and yeast genomes. Genome Res 8(6):590-8
9) Nitiss J and Wang JC  (1988) DNA topoisomerase-targeting antitumor drugs can be studied in yeast. Proc Natl Acad Sci U S A 85(20):7501-5
10) Avemann K, et al.  (1988) Camptothecin, a specific inhibitor of type I DNA topoisomerase, induces DNA breakage at replication forks. Mol Cell Biol 8(8):3026-34
11) Megonigal MD, et al.  (1997) Alterations in the catalytic activity of yeast DNA topoisomerase I result in cell cycle arrest and cell death. J Biol Chem 272(19):12801-8
12) Hann CL, et al.  (1998) Intragenic suppressors of mutant DNA topoisomerase I-induced lethality diminish enzyme binding of DNA. J Biol Chem 273(47):31519-27