Graeme Hewitt

ArticleVolume 86, Issue 7p1275-1292.e12Open access Affiliations & Notes 1College of Basic Medical Sciences, Medical Basic Research Innovation Center of Airway Disease in North China, Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun 130012, China 2Gene Center, Ludwig-Maximilians-Universität München, 81377 Munich, Germany 3Department of Biochemistry, Ludwig-Maximilians-Universität München, 81377 Munich, Germany 4Cancer Research UK Cambridge Institute,...

Tubbs A. Nussenzweig A. Endogenous DNA damage as a source of genomic instability in cancer. Cell. 2017; 168: 644-656 Ray Chaudhuri A. Nussenzweig A. The multifaceted roles of PARP1 in DNA repair and chromatin remodelling. Nat. Rev. Mol. Cell Biol. 2017; 18: 610-621 Farmer H. et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature. 2005; 434: 917-921 Bryant H.E. et al. Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature.

Highlights • Remodeling by ALC1 requires an acidic patch on the nucleosome entry side • A cryo-EM structure reveals how a regulatory linker segment binds to the acidic patch • Interfacial mutations compromise recruitment to DNA damage and catalytic activities Summary 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.