YKU80/YMR106C Summary Help

Standard Name YKU80 1
Systematic Name YMR106C
Alias HDF2 2
Feature Type ORF, Verified
Description Subunit of the telomeric Ku complex (Yku70p-Yku80p); involved in telomere length maintenance, structure and telomere position effect; required for localization of telomerase ribonucleoprotein via interaction with the TLC1 guide RNA; relocates to sites of double-strand cleavage to promote nonhomologous end joining during DSB repair (1, 3, 4, 5, 6, 7, 8 and see Summary Paragraph)
Name Description Yeast KU protein 1
Chromosomal Location
ChrXIII:480190 to 478301 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Gbrowse
Gene Ontology Annotations All YKU80 GO evidence and references
  View Computational GO annotations for YKU80
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 1 genes
Resources
Classical genetics
null
unspecified
Large-scale survey
null
Resources
213 total interaction(s) for 141 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 78
  • Affinity Capture-Western: 16
  • Co-crystal Structure: 1
  • Co-fractionation: 1
  • Co-purification: 1
  • Reconstituted Complex: 1
  • Two-hybrid: 6

Genetic Interactions
  • Dosage Growth Defect: 4
  • Dosage Lethality: 4
  • Dosage Rescue: 4
  • Negative Genetic: 19
  • Phenotypic Enhancement: 24
  • Phenotypic Suppression: 14
  • Positive Genetic: 4
  • Synthetic Growth Defect: 20
  • Synthetic Lethality: 10
  • Synthetic Rescue: 6

Resources
Expression Summary
histogram
Resources
Length (a.a.) 629
Molecular Weight (Da) 71,240
Isoelectric Point (pI) 4.99
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrXIII:480190 to 478301 | 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..1890 480190..478301 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 SGDIDS000004712
SUMMARY PARAGRAPH for YKU80

The Ku heterodimer is conserved in a wide range of eukaryotes and plays multiple roles in DNA metabolism (9). Composed in yeast of Yku70p and Yku80p, Ku functions in genome stability by participating in pathways for DNA double-strand break (DSB) repair via nonhomologous end-joining (NHEJ) and telomere maintenance (10, 1, 4). Ku is also involved in nuclear spatial organization and in the formation of gross chromosomal rearrangements (GCRs) including translocations, deletions, inversions, amplifications, and aneuploidy (5, 11, 12, 13, 14). Ku is a multifunctional protein that has distinct activities at DSBs and telomeres, including roles in the recruitment of telomerase and telomere length homeostasis (15, 16, 17), protection of telomeric ends from nucleolytic degradation and homologous recombination (18, 19, 20, 21), formation of telomeric heterochromatin leading to transcriptional silencing of nearby genes (19, 5, 6), late firing of replication origins near telomeres (22), and nuclear localization of telomeres (6).

In all eukaryotes, the Ku heterodimer is encoded by duplicate copies of an ancestral gene (12). The defining feature of Ku, observed in crystals of the human protein and inferred by conservation in yeast, is its central beta-barrel ring structure (23). Ku binds DNA by slipping the DSB end through this ring, which accounts for the substrate specificity of Ku as well as its ability to translocate along the DNA duplex. The Ku ring appears to bind ends in only one orientation, indicating an inherent polarity in its other domains (12). The C terminus of Yku80p is positioned toward the DSB end and makes a contact with Dnl4p that is important for NHEJ (24). The C terminus of Yku70p is oriented away from the DSB end. Correspondingly, this 25 amino acid region of Yku70p is required not for NHEJ but for telomere functions (25). In general, the yeast Ku C termini are more rudimentary than in higher eukaryotes, in that Yku80p lacks an alpha-helical bundle, whereas Yku70p lacks an SAP domain (23).

Inactivation of YKU70 or YKU80 results in telomere shortening, loss of telomere clustering and silencing, deregulation of the normally cell cycle-dependent telomeric G overhang, earlier activation of replication origins close to telomeres, and synthetic lethality with mutations that impair telomere replication (26, 27, 22, 18, 6, 19, 20). Certain yku80 C-terminal mutations have been shown to impair NHEJ while telomeric functions are retained (24). Conversely, yku80 alleles have been identified that are proficient in NHEJ but defective in specific aspects of telomeric function (17, 7). In humans, inactivation of either subunit of the Ku70-Ku80 heterodimer generates severe defects such as sensitivity to DNA damage, telomere shortening, and increased GCRs that are frequently observed in many cancers (13).

Last updated: 2007-05-25 Contact SGD

References cited on this page View Complete Literature Guide for YKU80
1) Boulton SJ and Jackson SP  (1996) Identification of a Saccharomyces cerevisiae Ku80 homologue: roles in DNA double strand break rejoining and in telomeric maintenance. Nucleic Acids Res 24(23):4639-48
2) Feldmann H, et al.  (1996) HDF2, the second subunit of the Ku homologue from Saccharomyces cerevisiae. J Biol Chem 271(44):27765-9
3) Martin SG, et al.  (1999) Relocalization of telomeric Ku and SIR proteins in response to DNA strand breaks in yeast. Cell 97(5):621-33
4) Milne GT, et al.  (1996) Mutations in two Ku homologs define a DNA end-joining repair pathway in Saccharomyces cerevisiae. Mol Cell Biol 16(8):4189-98
5) Boulton SJ and Jackson SP  (1998) Components of the Ku-dependent non-homologous end-joining pathway are involved in telomeric length maintenance and telomeric silencing. EMBO J 17(6):1819-28
6) Laroche T, et al.  (1998) Mutation of yeast Ku genes disrupts the subnuclear organization of telomeres. Curr Biol 8(11):653-6
7) Bertuch AA and Lundblad V  (2003) The Ku heterodimer performs separable activities at double-strand breaks and chromosome termini. Mol Cell Biol 23(22):8202-15
8) Dalby AB, et al.  (2013) RNA recognition by the DNA end-binding Ku heterodimer. RNA 19(6):841-51
9) Corda Y, et al.  (2005) Inactivation of Ku-mediated end joining suppresses mec1Delta lethality by depleting the ribonucleotide reductase inhibitor Sml1 through a pathway controlled by Tel1 kinase and the Mre11 complex. Mol Cell Biol 25(23):10652-64
10) Bertuch AA and Lundblad V  (2003) Which end: dissecting Ku's function at telomeres and double-strand breaks. Genes Dev 17(19):2347-50
11) Taddei A, et al.  (2004) Separation of silencing from perinuclear anchoring functions in yeast Ku80, Sir4 and Esc1 proteins. EMBO J 23(6):1301-12
12) Daley JM, et al.  (2005) Nonhomologous end joining in yeast. Annu Rev Genet 39():431-51
13) Banerjee S, et al.  (2006) Suppression of gross chromosomal rearrangements by yKu70-yKu80 heterodimer through DNA damage checkpoints. Proc Natl Acad Sci U S A 103(6):1816-21
14) Ribes-Zamora A, et al.  (2007) Distinct faces of the Ku heterodimer mediate DNA repair and telomeric functions. Nat Struct Mol Biol 14(4):301-7
15) Fisher TS, et al.  (2004) Cell cycle-dependent regulation of yeast telomerase by Ku. Nat Struct Mol Biol 11(12):1198-205
16) Porter SE, et al.  (1996) The DNA-binding protein Hdf1p (a putative Ku homologue) is required for maintaining normal telomere length in Saccharomyces cerevisiae. Nucleic Acids Res 24(4):582-5
17) Stellwagen AE, et al.  (2003) Ku interacts with telomerase RNA to promote telomere addition at native and broken chromosome ends. Genes Dev 17(19):2384-95
18) Gravel S, et al.  (1998) Yeast Ku as a regulator of chromosomal DNA end structure. Science 280(5364):741-4
19) Nugent CI, et al.  (1998) Telomere maintenance is dependent on activities required for end repair of double-strand breaks. Curr Biol 8(11):657-60
20) Polotnianka RM, et al.  (1998) The yeast Ku heterodimer is essential for protection of the telomere against nucleolytic and recombinational activities. Curr Biol 8(14):831-4
21) Maringele L and Lydall D  (2002) EXO1-dependent single-stranded DNA at telomeres activates subsets of DNA damage and spindle checkpoint pathways in budding yeast yku70Delta mutants. Genes Dev 16(15):1919-33
22) Cosgrove AJ, et al.  (2002) Ku complex controls the replication time of DNA in telomere regions. Genes Dev 16(19):2485-90
23) Walker JR, et al.  (2001) Structure of the Ku heterodimer bound to DNA and its implications for double-strand break repair. Nature 412(6847):607-14
24) Palmbos PL, et al.  (2005) Mutations of the Yku80 C terminus and Xrs2 FHA domain specifically block yeast nonhomologous end joining. Mol Cell Biol 25(24):10782-90
25) Driller L, et al.  (2000) A short C-terminal domain of Yku70p is essential for telomere maintenance. J Biol Chem 275(32):24921-7
26) Barnes G and Rio D  (1997) DNA double-strand-break sensitivity, DNA replication, and cell cycle arrest phenotypes of Ku-deficient Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 94(3):867-72
27) Boulton SJ and Jackson SP  (1996) Saccharomyces cerevisiae Ku70 potentiates illegitimate DNA double-strand break repair and serves as a barrier to error-prone DNA repair pathways. EMBO J 15(18):5093-103