title: Human ISWI complexes are targeted by SMARCA5 ATPase and SLIDE domains to help resolve lesion-stalled transcription.
abstract: Chromatin compaction of deoxyribonucleic acid (DNA) presents a major challenge to the detection and removal of DNA damage. Helix-distorting DNA lesions that block transcription are specifically repaired by transcription-coupled nucleotide excision repair, which is initiated by binding of the CSB protein to lesion-stalled RNA polymerase II. Using live cell imaging, we identify a novel function for two distinct mammalian ISWI adenosine triphosphate (ATP)-dependent chromatin remodeling complexes in resolving lesion-stalled transcription. Human ISWI isoform SMARCA5/SNF2H and its binding partners ACF1 and WSTF are rapidly recruited to UV-C induced DNA damage to specifically facilitate CSB binding and to promote transcription recovery. SMARCA5 targeting to UV-C damage depends on transcription and histone modifications and requires functional SWI2/SNF2-ATPase and SLIDE domains. After initial recruitment to UV damage, SMARCA5 re-localizes away from the center of DNA damage, requiring its HAND domain. Our studies support a model in which SMARCA5 targeting to DNA damage-stalled transcription sites is controlled by an ATP-hydrolysis-dependent scanning and proofreading mechanism, highlighting how SWI2/SNF2 chromatin remodelers identify and bind nucleosomes containing damaged DNA.
authors.affiliation: Department of Genetics, Medical Genetics Cluster, Cancer Genomics Netherlands, Erasmus MC, Rotterdam, 3015 GE, The Netherlands.
authors.forename: Özge Z
authors.initials: ÖZ
authors.lastname: Aydin
authors.affiliation: Department of Genetics, Medical Genetics Cluster, Cancer Genomics Netherlands, Erasmus MC, Rotterdam, 3015 GE, The Netherlands.
authors.forename: Jurgen A
authors.initials: JA
authors.lastname: Marteijn
authors.affiliation: Department of Genetics, Medical Genetics Cluster, Cancer Genomics Netherlands, Erasmus MC, Rotterdam, 3015 GE, The Netherlands.
authors.forename: Cristina
authors.initials: C
authors.lastname: Ribeiro-Silva
authors.affiliation: Department of Genetics, Medical Genetics Cluster, Cancer Genomics Netherlands, Erasmus MC, Rotterdam, 3015 GE, The Netherlands.
authors.forename: Aida
authors.initials: A
authors.lastname: Rodríguez López
authors.affiliation: Department of Genetics, Medical Genetics Cluster, Cancer Genomics Netherlands, Erasmus MC, Rotterdam, 3015 GE, The Netherlands.
authors.forename: Nils
authors.initials: N
authors.lastname: Wijgers
authors.affiliation: Department of Toxicogenetics, Leiden University Medical Center, Leiden, 2333 ZC, The Netherlands.
authors.forename: Godelieve
authors.initials: G
authors.lastname: Smeenk
authors.affiliation: Department of Toxicogenetics, Leiden University Medical Center, Leiden, 2333 ZC, The Netherlands.
authors.forename: Haico
authors.initials: H
authors.lastname: van Attikum
authors.affiliation: Department of Cell Biology, Medical Genetics Cluster, Erasmus MC, Rotterdam, 3015 GE, The Netherlands.
authors.forename: Raymond A
authors.initials: RA
authors.lastname: Poot
authors.affiliation: Department of Genetics, Medical Genetics Cluster, Cancer Genomics Netherlands, Erasmus MC, Rotterdam, 3015 GE, The Netherlands.
authors.forename: Wim
authors.initials: W
authors.lastname: Vermeulen
authors.affiliation: Department of Genetics, Medical Genetics Cluster, Cancer Genomics Netherlands, Erasmus MC, Rotterdam, 3015 GE, The Netherlands w.lans@erasmusmc.nl.
authors.forename: Hannes
authors.identifier: http://orcid.org/0000-0003-4417-5358
authors.initials: H
authors.lastname: Lans
mesh_terms: D000251:Adenosine Triphosphatases / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D042002:Chromatin Assembly and Disassembly; D002868:Chromosomal Proteins, Non-Histone / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D004249:DNA Damage; D004265:DNA Helicases / Q000378:metabolism; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D000075223:Poly-ADP-Ribose Binding Proteins; D017434:Protein Structure, Tertiary; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D014466:Ultraviolet Rays; D000092468:Bromodomain Containing Proteins
chemical_list: D000251:Adenosine Triphosphatases; D002868:Chromosomal Proteins, Non-Histone; D004265:DNA Helicases; D045643:DNA Repair Enzymes; D006657:Histones; D000075223:Poly-ADP-Ribose Binding Proteins; D014157:Transcription Factors; C492319:BAZ1A protein, human; D000092468:Bromodomain Containing Proteins; C116750:BAZ1B protein, human; C409462:SMARCA5 protein, human; C078673:ERCC6 protein, human