Disease relevance of INO80

• Mutants of ino80 show hypersensitivity to agents that cause DNA damage, in addition to defects in transcription [1].

High impact information on INO80

• Finally, components of the INO80 complex show synthetic genetic interactions with the RAD52 DNA repair pathway, the main pathway for DSB repair in yeast [2].
• Finally, we demonstrate that conversion of the DSB into ssDNA is compromised in arp8 and H2A mutants, which are both deficient for INO80 activity at the site of damage [3].
• This interaction requires Nhp10, an HMG-like subunit of the INO80 complex [2].
• The INO80 complex is recruited to a HO endonuclease-induced DSB through a specific interaction with the DNA damage-induced phosphorylated histone H2A (gamma-H2AX) [2].
• The budding yeast INO80 complex is a conserved ATP-dependent nucleosome remodeler containing actin-related proteins Arp5 and Arp8 [3].

Biological context of INO80

• In silico characterization of the INO80 subfamily of SWI2/SNF2 chromatin remodeling proteins [4].
• These results indicate that chromatin remodelling driven by the Ino80 ATPase may be connected to transcription as well as DNA damage repair [1].
• In ino80 null mutants, gene activation mediated by an ICRE decreased to 16% of the wild-type level [5].
• Mutation of the Ino80p lysine residue corresponding to the NTP binding site of Snf2p led to a non-functional protein [5].
• Nevertheless, SNF2 in increased gene dosage did not suppress ino80 mutant phenotypes [5].

Associations of INO80 with chemical compounds

• We identified the ino80 mutation causing inositol auxotrophy as a result of a defect in ICRE-dependent gene activation [5].
• Inositol hexakisphosphate (IP6) inhibits nucleosome mobilization by NURF, ISW2, and INO80 complexes [6].
• In arg82 mutant strains, remodeling of PHO5 promoter chromatin is impaired, and the adenosine triphosphate-dependent chromatin-remodeling complexes SWI/SNF and INO80 are not efficiently recruited to phosphate-responsive promoters [7].

Physical interactions of INO80

• The INO80 complex contains about 12 polypeptides including two proteins related to the bacterial RuvB DNA helicase, which catalyses branch migration of Holliday junctions [1].

Other interactions of INO80

• Loss of Rvb1p or Ino80p affects many yeast promoters similarly [8].
• Swr1p and six other subunits were found only in SWR1-Com, whereas six other subunits were also found in the NuA4 histone acetyltransferase and/or the Ino80 chromatin remodeling complex [9].
• Yet, mutants lacking SWR or INO80 remain checkpoint competent, whereas loss of NuA4-dependent histone acetylation leads to G1 checkpoint persistence, suggesting that H2A phosphorylation promotes two independent events, rapid Rad9 recruitment to DSBs and subsequent remodeling by NuA4, SWR, and INO80 [10].
• Anc1 interacts with the catalytic subunits of the general transcription factors TFIID and TFIIF, the chromatin remodeling complexes RSC and INO80, and the histone acetyltransferase complex NuA3 [11].

Analytical, diagnostic and therapeutic context of INO80

• As demonstrated by gel filtration, Ino80p is part of a high-molecular-weight complex of more than 1 MDa [5].

References