The INO80 subfamily of chromatin remodeling complexes are ATPases, and includes the INO80 and SWR1 complexes.[1][2]

Function edit

One of the main roles of the INO80 subfamily is the incorporation and removal of alternate histones in the nucleosome.[1] In the presence of the H2A.Z histone, the INO80 subfamily of remodelers catalyze the repositioning and eventual removal of this alternate histone.[3] The H2A.Z histone is found on the first nucleosome at the beginning of genes.[3] The INO80 subfamily of remodelers will also be recruited to the H2A.X histone in the homologous recombination repair pathway.[3]

In addition to this function, the INO80 subfamily plays a role in transcriptional regulation and genomic recombination.[4] In the DNA damage pathways, the INO80 subfamily aids in repair, recombination, and cell cycle regulation.[4] The INO80 subfamily can activate the recruitment of replication checkpoint factors and can aid in the recovery from replicative stress on the DNA strand.[4] The subfamily’s ability to incorporate alternate histones is important for genome stability, disease pathogenesis, and stem cell identity.[4] INO80 complexes commonly bind to nucleosome free regions at transcription start sites and termination sites.[2] INO80 is the only remodeler that is able to use the energy from ATP hydrolysis to create nucleosome free regions and cooperate with other remodelers to equally space nucleosomes.[3]

Structure edit

Chromatin remodelers in the INO80 subfamily are made of multiple subunit complexes with split ATPase domains.[3] The INO80 subfamily's protein domains are an N-terminus, two RuvB-like proteins (Rvb1 and Rvb2), and a C-terminus.[1] The ATPase domain of the N-terminus functions in the identification of DNA damage and aids in the stability of telomeres.[4] A long insertion in the ATPase domain is what recruits the Rvb1 and Rvb2 helicases.[2] These helicases contribute to genome maintenance and are unique to the INO80 subfamily of chromatin remodeling complexes.[4] This subfamily also contains an Arp4-actin complex that aids in stability of genes.[2] The Arp5 subunit is required for ATPase function, binding to the DNA, and relocation of nucleosomes.[3]

References edit

  1. ^ a b c Clapier, Cedric R.; Iwasa, Janet; Cairns, Bradley R.; Peterson, Craig L. (July 2017). "Mechanisms of action and regulation of ATP-dependent chromatin-remodelling complexes". Nature Reviews Molecular Cell Biology. 18 (7): 407–422. doi:10.1038/nrm.2017.26. ISSN 1471-0072. PMC 8127953. PMID 28512350.
  2. ^ a b c d Poli, Jérôme; Gasser, Susan M.; Papamichos-Chronakis, Manolis (2017-10-05). "The INO80 remodeller in transcription, replication and repair". Philosophical Transactions of the Royal Society B: Biological Sciences. 372 (1731): 20160290. doi:10.1098/rstb.2016.0290. ISSN 0962-8436. PMC 5577468. PMID 28847827.
  3. ^ a b c d e f Yen, Kuangyu; Vinayachandran, Vinesh; Pugh, B. Franklin (September 2013). "SWR-C and INO80 Chromatin Remodelers Recognize Nucleosome-free Regions Near +1 Nucleosomes". Cell. 154 (6): 1246–1256. doi:10.1016/j.cell.2013.08.043. PMC 4090706. PMID 24034248.
  4. ^ a b c d e f Morrison, Ashby J. (2017-10-05). "Genome maintenance functions of the INO80 chromatin remodeller". Philosophical Transactions of the Royal Society B: Biological Sciences. 372 (1731): 20160289. doi:10.1098/rstb.2016.0289. ISSN 0962-8436. PMC 5577467. PMID 28847826.