Human ISWI complexes are targeted by SMARCA5 ATPase and SLIDE domains to help resolve lesion-stalled transcription.

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.

[1]  G. Hong,et al.  Nucleic Acids Research , 2015, Nucleic Acids Research.

[2]  T. Ideker,et al.  A UV-induced genetic network links the RSC complex to nucleotide excision repair and shows dose-dependent rewiring. , 2013, Cell reports.

[3]  O. Schärer.  Nucleotide excision repair in eukaryotes. , 2013, Cold Spring Harbor perspectives in biology.

[4]  Lei Zhong,et al.  SIRT6 recruits SNF2H to DNA break sites, preventing genomic instability through chromatin remodeling. , 2013, Molecular cell.

[5]  W. V. van Cappellen,et al.  Enhanced chromatin dynamics by FACT promotes transcriptional restart after UV-induced DNA damage. , 2013, Molecular cell.

[6]  W. Vermeulen,et al.  Mammalian transcription-coupled excision repair. , 2013, Cold Spring Harbor perspectives in biology.

[7]  G. Giglia-Mari,et al.  Histone Methyltransferase DOT1L Drives Recovery of Gene Expression after a Genotoxic Attack , 2013, PLoS genetics.

[8]  R. Lake,et al.  ATP-Dependent Chromatin Remodeling by Cockayne Syndrome Protein B and NAP1-Like Histone Chaperones Is Required for Efficient Transcription-Coupled DNA Repair , 2013, PLoS genetics.

[9]  N. Mailand,et al.  Poly(ADP-ribosyl)ation links the chromatin remodeler SMARCA5/SNF2H to RNF168-dependent DNA damage signaling , 2013, Journal of Cell Science.

[10]  X. Zhuang,et al.  Nucleosome mobilization by ISW2 requires the concerted action of the ATPase and SLIDE domains , 2013, Nature Structural &Molecular Biology.

[11]  W. Vermeulen,et al.  PARP1 promotes nucleotide excision repair through DDB2 stabilization and recruitment of ALC1 , 2012, The Journal of cell biology.

[12]  Jeroen A. A. Demmers,et al.  UV-sensitive syndrome protein UVSSA recruits USP7 to regulate transcription-coupled repair , 2012, Nature Genetics.

[13]  W. Vermeulen,et al.  ATP-dependent chromatin remodeling in the DNA-damage response , 2012, Epigenetics & Chromatin.

[14]  Geoffrey J. Barton,et al.  A Role for Snf2-Related Nucleosome-Spacing Enzymes in Genome-Wide Nucleosome Organization , 2011, Science.

[15]  H. Schiessel,et al.  Kinetic proofreading in chromatin remodeling: the case of ISWI/ACF. , 2011, Biophysical journal.

[16]  H. van Attikum,et al.  Chromatin and the DNA damage response: The cancer connection , 2011, Molecular oncology.

[17]  W. Vermeulen.  Dynamics of mammalian NER proteins. , 2011, DNA repair.

[18]  H. Leonhardt,et al.  Role for hACF1 in the G2/M damage checkpoint , 2011, Nucleic acids research.

[19]  T. Kleinberger,et al.  The adenovirus E4orf4 protein targets PP2A to the ACF chromatin-remodeling factor and induces cell death through regulation of SNF2h-containing complexes , 2011, Nucleic acids research.

[20]  Raffaele Giancarlo,et al.  Genome‐wide characterization of chromatin binding and nucleosome spacing activity of the nucleosome remodelling ATPase ISWI , 2011, The EMBO journal.

[21]  T. Richmond,et al.  Structure and mechanism of the chromatin remodelling factor ISW1a , 2011, Nature.

[22]  H. Tauchi,et al.  Regulation of homologous recombination by RNF20-dependent H2B ubiquitination. , 2011, Molecular cell.

[23]  Satoshi Nakajima,et al.  The ACF1 complex is required for DNA double-strand break repair in human cells. , 2010, Molecular cell.

[24]  S. Sarkar,et al.  The Ino80 chromatin-remodeling complex restores chromatin structure during UV DNA damage repair , 2010, The Journal of cell biology.

[25]  K. Rippe,et al.  Human ISWI chromatin-remodeling complexes sample nucleosomes via transient binding reactions and become immobilized at active sites , 2010, Proceedings of the National Academy of Sciences.

[26]  G. Narlikar,et al.  A proposal for kinetic proof reading by ISWI family chromatin remodeling motors. , 2010, Current opinion in chemical biology.

[27]  Lei Li,et al.  INO80 chromatin remodeling complex promotes the removal of UV lesions by the nucleotide excision repair pathway , 2010, Proceedings of the National Academy of Sciences.

[28]  A. Lehmann,et al.  A semi-automated non-radioactive system for measuring recovery of RNA synthesis and unscheduled DNA synthesis using ethynyluracil derivatives. , 2010, DNA repair.

[29]  J. Hoeijmakers,et al.  Involvement of Global Genome Repair, Transcription Coupled Repair, and Chromatin Remodeling in UV DNA Damage Response Changes during Development , 2010, PLoS genetics.

[30]  K. Sugasawa.  Regulation of damage recognition in mammalian global genomic nucleotide excision repair. , 2010, Mutation research.

[31]  R. Lake,et al.  UV-induced association of the CSB remodeling protein with chromatin requires ATP-dependent relief of N-terminal autorepression. , 2010, Molecular cell.

[32]  Yifan Cheng,et al.  The chromatin remodeler ACF acts as a dimeric motor to space nucleosomes , 2009, Nature.

[33]  Michael D. Stone,et al.  Dynamics of nucleosome remodelling by individual ACF complexes , 2009, Nature.

[34]  J. Hoeijmakers.  DNA damage, aging, and cancer. , 2009, The New England journal of medicine.

[35]  Qian Zhang,et al.  The chromatin remodeling factor BRG1 stimulates nucleotide excision repair by facilitating recruitment of XPC to sites of DNA damage , 2009, Cell cycle.

[36]  J. Bartek,et al.  The DNA-damage response in human biology and disease , 2009, Nature.

[37]  G. Wani,et al.  Human SNF5/INI1, a Component of the Human SWI/SNF Chromatin Remodeling Complex, Promotes Nucleotide Excision Repair by Influencing ATM Recruitment and Downstream H2AX Phosphorylation , 2009, Molecular and Cellular Biology.

[38]  G. Wani,et al.  Modulation of Nucleotide Excision Repair by Mammalian SWI/SNF Chromatin-remodeling Complex* , 2009, The Journal of Biological Chemistry.

[39]  Vamsi K. Gangaraju,et al.  Conformational changes associated with template commitment in ATP-dependent chromatin remodeling by ISW2. , 2009, Molecular cell.

[40]  B. Cairns,et al.  The biology of chromatin remodeling complexes. , 2009, Annual review of biochemistry.

[41]  C. Thiemermann,et al.  Imidazoquinolinone, Imidazopyridine, and Isoquinolindione Derivatives as Novel and Potent Inhibitors of the Poly(ADP-ribose) Polymerase (PARP): A Comparison with Standard PARP Inhibitors , 2008, Molecular Pharmacology.

[42]  P. Hanawalt,et al.  Transcription-coupled DNA repair: two decades of progress and surprises , 2008, Nature Reviews Molecular Cell Biology.

[43]  A. Houtsmuller,et al.  Versatile DNA damage detection by the global genome nucleotide excision repair protein XPC , 2008, Journal of Cell Science.

[44]  K. Murakami.  Faculty Opinions recommendation of Structural basis of transcription inhibition by alpha-amanitin and implications for RNA polymerase II translocation. , 2008 .

[45]  R. Kingston,et al.  Diverse regulation of SNF2h chromatin remodeling by noncatalytic subunits. , 2008, Biochemistry.

[46]  B. Bartholomew,et al.  Domain Architecture of the Catalytic Subunit in the ISW2-Nucleosome Complex , 2007, Molecular and Cellular Biology.

[47]  W. V. van Cappellen,et al.  Activation of multiple DNA repair pathways by sub-nuclear damage induction methods , 2007, Journal of Cell Science.

[48]  M. Smerdon,et al.  Rad4–Rad23 interaction with SWI/SNF links ATP-dependent chromatin remodeling with nucleotide excision repair , 2006, Nature Structural &Molecular Biology.

[49]  M. Lazar,et al.  The N‐CoR complex enables chromatin remodeler SNF2H to enhance repression by thyroid hormone receptor , 2006, The EMBO journal.

[50]  W. Vermeulen,et al.  Cockayne syndrome A and B proteins differentially regulate recruitment of chromatin remodeling and repair factors to stalled RNA polymerase II in vivo. , 2006, Molecular cell.

[51]  H. Horvitz,et al.  C. elegans ISWI and NURF301 antagonize an Rb-like pathway in the determination of multiple cell fates , 2006, Development.

[52]  M. Pazin,et al.  Histone H4-K16 Acetylation Controls Chromatin Structure and Protein Interactions , 2006, Science.

[53]  Raymond A. Poot,et al.  The Williams syndrome transcription factor interacts with PCNA to target chromatin remodelling by ISWI to replication foci , 2004, Nature Cell Biology.

[54]  I. Vetter,et al.  ACF1 improves the effectiveness of nucleosome mobilization by ISWI through PHD–histone contacts , 2004, The EMBO journal.

[55]  C. Menck,et al.  CPD-photolyase adenovirus-mediated gene transfer in normal and DNA-repair-deficient human cells , 2004, Journal of Cell Science.

[56]  W. V. van Cappellen,et al.  DNA damage stabilizes interaction of CSB with the transcription elongation machinery , 2004, The Journal of cell biology.

[57]  M. Zofall,et al.  Topography of the ISW2–nucleosome complex: insights into nucleosome spacing and chromatin remodeling , 2004, The EMBO journal.

[58]  Stuart L Schreiber,et al.  Methylation of histone H3 K4 mediates association of the Isw1p ATPase with chromatin. , 2003, Molecular cell.

[59]  M. J. Moné,et al.  Xeroderma Pigmentosum Group A Protein Loads as a Separate Factor onto DNA Lesions , 2003, Molecular and Cellular Biology.

[60]  C. Müller,et al.  Crystal structure and functional analysis of a nucleosome recognition module of the remodeling factor ISWI. , 2003, Molecular cell.

[61]  R. Poot,et al.  An ACF1–ISWI chromatin-remodeling complex is required for DNA replication through heterochromatin , 2002, Nature Genetics.

[62]  P. Wade,et al.  WSTF–ISWI chromatin remodeling complex targets heterochromatic replication foci , 2002, The EMBO journal.

[63]  J. Tamkun,et al.  Modulation of ISWI function by site‐specific histone acetylation , 2002, EMBO reports.

[64]  G. Längst,et al.  ISWI induces nucleosome sliding on nicked DNA. , 2001, Molecular cell.

[65]  M. J. Moné,et al.  Sequential assembly of the nucleotide excision repair factors in vivo. , 2001, Molecular cell.

[66]  Y. Kaneda,et al.  ATP‐dependent chromatin remodeling facilitates nucleotide excision repair of UV‐induced DNA lesions in synthetic dinucleosomes , 2001, The EMBO journal.

[67]  G. Längst,et al.  Critical Role for the Histone H4 N Terminus in Nucleosome Remodeling by ISWI , 2001, Molecular and Cellular Biology.

[68]  R. Kingston,et al.  ATP-Dependent Chromatin Remodeling by the Cockayne Syndrome B DNA Repair-Transcription-Coupling Factor , 2000, Molecular and Cellular Biology.

[69]  R. Poot,et al.  HuCHRAC, a human ISWI chromatin remodelling complex contains hACF1 and two novel histone‐fold proteins , 2000, The EMBO journal.

[70]  D. Reinberg,et al.  Purification and Characterization of a Human Factor That Assembles and Remodels Chromatin* , 2000, The Journal of Biological Chemistry.

[71]  D. Trono,et al.  A Third-Generation Lentivirus Vector with a Conditional Packaging System , 1998, Journal of Virology.

[72]  Y. Nakamura,et al.  Cloning and mapping of SMARCA5 encoding hSNF2H, a novel human homologue of Drosophila ISWI , 1998, Cytogenetic and Genome Research.

[73]  M. Mathews,et al.  Transcription elongation factor P-TEFb is required for HIV-1 tat transactivation in vitro. , 1997, Genes & development.

[74]  J. Hoeijmakers,et al.  The Cockayne syndrome B protein, involved in transcription‐coupled DNA repair, resides in an RNA polymerase II‐containing complex , 1997, The EMBO journal.

[75]  Ryuji Kobayashi,et al.  ACF, an ISWI-Containing and ATP-Utilizing Chromatin Assembly and Remodeling Factor , 1997, Cell.

[76]  G. Almouzni,et al.  Transcription Recovery after DNA Damage Requires Chromatin Priming by the H3.3 Histone Chaperone HIRA , 2013, Cell.

[77]  Paul Tempst,et al.  WSTF regulates the H2A.X DNA damage response via a novel tyrosine kinase , 2009 .