Recruitment of the INO80 complex by H2A phosphorylation links ATP-dependent chromatin remodeling with DNA double-strand break repair.

By Haico van Attikum, Olivier Fritsch, B. Hohn, S. Gasser. Cell, 2004

677 citations recorded by the source corpus.

The budding yeast INO80 complex is a conserved ATP-dependent nucleosome remodeler containing actin-related proteins Arp5 and Arp8. Strains lacking INO80, ARP5, or ARP8 have defects in transcription. Here we show that these mutants are hypersensitive to DNA damaging agents and to double-strand breaks (DSBs) induced by the HO endonuclease. The checkpoint response and most transcriptional modulation associated with induction of DNA damage are unaffected by these mutations. Using chromatin immunoprecipitation we show that Ino80, Arp5, and Arp8 are recruited to an HO-induced DSB, where a phosphorylated form of H2A accumulates. Recruitment of Ino80 is compromised in cells lacking the H2A phosphoacceptor S129. 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. These results implicate INO80-mediated chromatin remodeling directly at DSBs, where it appears to facilitate processing of the lesion.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/aba4acacd7bd952d748d6c4972c180a1fb7fd4ce

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Molecular Biology

Citations in the corpus

Dynamics of DNA damage response proteins at DNA breaks: a focus on protein modifications. (2011, background): “Phosphorylated H2AX also promotes the recruitment of chromatinmodifying complexes, including yeast NuA4, INO80, and SWR1; Drosophila Tip60; and human p400 (Downs et al. 2004; Kusch et al. 2004; Morrison et al. 2004; van Attikum et al. 2004, 2007; Xu et al. 2010).”
Sgs1 helicase and two nucleases Dna2 and Exo1 resect DNA double strand break ends (2008, neutral): “... proteins that are required for a normal rate of DSB end resection have been identified in budding yeast and mammals including the MRX/MRN complex (Mre11-Rad50-Xrs2 in yeast and Mre11-Rad50-Nbs1 in human) (Ivanov et al., 1994; Jazayeri et al., 2006), Sae2/CtIP (Clerici et al., 2005; Sartori et al”
The γ‐H2A.X: Is it just a surrogate marker of double‐strand breaks or much more? (2008, background): “X [Downs et al., 2004; Kusch et al., 2004; Morrison et al., 2004; van Attikum et al., 2004; Stucki et al., 2005]. c-H2A.”
The biology of chromatin remodeling complexes. (2009, background): “INO80 action may help expose DNA near the DSB to 5′-3′ resection, as ino80 mutants fail to create the 3′ single-stranded DNA overhang, a critical step in DNA repair (88).”
Surviving the breakup: the DNA damage checkpoint. (2006, background): “A major role for γ-H2AX is the recruitment of chromatin remodelers, including the Ino80, Rvb1, NuA4, and Swr1 complexes to the DSB (12, 17, 35, 97, 110, 147).”
γ-H2AX Dephosphorylation by Protein Phosphatase 2A Facilitates DNA Double-Strand Break Repair (2005, background): “However, recent studies have implicated two SNF2-family ATPase complexes in removing g-yH2A and g-H2AX by histone exchange: Ino80 in S. cerevisiae (Downs et al., 2004; Morrison et al., 2004; van Attikum et al., 2004 ) and dTip60 in Drosophila (Kusch et al., 2004), respectively.”
Chromatin challenges during DNA replication and repair. (2007, neutral): “…INO80 and SWR1 chromatin-remodeling complexes, likely in conjunction with the NuA4 HAT, all of which are recruited to the break partly through their binding to g -H2AX itself (Bird et al., 2002; Downs et al., 2004; Morrison et al., 2004; Papamichos-Chronakis et al., 2006; van Attikum et al., 2004).”