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Mechanistic Insights into Regulation of the ALC1 Remodeler by the Nucleosome Acidic Patch.

<div class='caption-title'>(A) Left: octamer surface colored by electrostatic potential (from –5 kB T/e, indicated in red, to +5 kB T/e, indicated in blue). Right: key residues of the H2A AP. Based on PDB: 1AOI.</div>
<div class='caption-title'>(A) ALC1fl-histone cross-links. Magenta lines indicate linker-histone cross-links: gray lines indicate other cross-links.</div>
<div class='caption-title'>(A) ATPase activity for 20 μM ALC1fl R860W or ALC1fl R611A/S612A/R860W in the presence of 2 μM WT/WT nucleosomes. Error bars represent SD (n = 3 independent experiments).</div>
Lehmann LC, Bacic L, Hewitt G, Brackmann K, Sabantsev A, Gaullier G, Pytharopoulou S, Degliesposti G, Okkenhaug H, Tan S, Costa A, Skehel JM, Boulton SJ, Deindl S
OpenAccess logo Cell Rep 33 108529 (2020)
Cited: 16 times
EuropePMC logo PMID: 33357431

Abstract

Upon DNA damage, the ALC1/CHD1L nucleosome remodeling enzyme (remodeler) is activated by binding to poly(ADP-ribose). How activated ALC1 recognizes the nucleosome, as well as how this recognition is coupled to remodeling, is unknown. Here, we show that remodeling by ALC1 requires a wild-type acidic patch on the entry side of the nucleosome. The cryo-electron microscopy structure of a nucleosome-ALC1 linker complex reveals a regulatory linker segment that binds to the acidic patch. Mutations within this interface alter the dynamics of ALC1 recruitment to DNA damage and impede the ATPase and remodeling activities of ALC1. Full activation requires acidic patch-linker segment interactions that tether the remodeler to the nucleosome and couple ATP hydrolysis to nucleosome mobilization. Upon DNA damage, such a requirement may be used to modulate ALC1 activity via changes in the nucleosome acidic patches.

Articles - 6zhy mentioned but not cited (3)

  1. Mechanistic Insights into Regulation of the ALC1 Remodeler by the Nucleosome Acidic Patch. Lehmann LC, Bacic L, Hewitt G, Brackmann K, Sabantsev A, Gaullier G, Pytharopoulou S, Degliesposti G, Okkenhaug H, Tan S, Costa A, Skehel JM, Boulton SJ, Deindl S. Cell Rep 33 108529 (2020)
  2. Reorientation of INO80 on hexasomes reveals basis for mechanistic versatility. Wu H, Muñoz EN, Hsieh LJ, Chio US, Gourdet MA, Narlikar GJ, Cheng Y. Science 381 319-324 (2023)
  3. 16S rDNA-based phylogeny of non-symbiotic bacteria of Entorno-pathogenic nematodes from infected insect cadavers. Razia M, Karthikraja R, Padmanaban K, Chellapandi P, Sivaramakrishnan S. Genomics Proteomics Bioinformatics 9 104-112 (2011)


Reviews citing this publication (4)

  1. Principles of nucleosome recognition by chromatin factors and enzymes. McGinty RK, Tan S. Curr Opin Struct Biol 71 16-26 (2021)
  2. PARP Power: A Structural Perspective on PARP1, PARP2, and PARP3 in DNA Damage Repair and Nucleosome Remodelling. van Beek L, McClay É, Patel S, Schimpl M, Spagnolo L, Maia de Oliveira T. Int J Mol Sci 22 5112 (2021)
  3. Sophisticated Conversations between Chromatin and Chromatin Remodelers, and Dissonances in Cancer. Clapier CR. Int J Mol Sci 22 5578 (2021)
  4. Energy-driven genome regulation by ATP-dependent chromatin remodellers. Eustermann S, Patel AB, Hopfner KP, He Y, Korber P. Nat Rev Mol Cell Biol 25 309-332 (2024)

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