title: NAP1L1 accelerates activation and decreases pausing to enhance nucleosome remodeling by CSB.
abstract: Cockayne syndrome protein B (CSB) belongs to the SWI2/SNF2 ATP-dependent chromatin remodeler family, and CSB is the only ATP-dependent chromatin remodeler essential for transcription-coupled nucleotide excision DNA repair. CSB alone remodels nucleosomes ∼10-fold slower than the ACF remodeling complex. Strikingly, NAP1-like histone chaperones interact with CSB and greatly enhance CSB-mediated chromatin remodeling. While chromatin remodeling by CSB and NAP1-like proteins is crucial for efficient transcription-coupled DNA repair, the mechanism by which NAP1-like proteins enhance chromatin remodeling by CSB remains unknown. Here we studied CSB's DNA-binding and nucleosome-remodeling activities at the single molecule level in real time. We also determined how the NAP1L1 chaperone modulates these activities. We found that CSB interacts with DNA in two principle ways: by simple binding and a more complex association that involves gross DNA distortion. Remarkably, NAP1L1 suppresses both these interactions. Additionally, we demonstrate that nucleosome remodeling by CSB consists of three distinct phases: activation, translocation and pausing, similar to ACF. Importantly, we found that NAP1L1 promotes CSB-mediated remodeling by accelerating both activation and translocation. Additionally, NAP1L1 increases CSB processivity by decreasing the pausing probability during translocation. Our study, therefore, uncovers the different steps of CSB-mediated chromatin remodeling that can be regulated by NAP1L1.
authors.affiliation: Department of Physics and Astronomy, Seoul National University, Seoul 08826, Republic of Korea.|Institute of Applied Physics, Seoul National University, Seoul 08826, Republic of Korea.|National Center of Creative Research Initiatives, Seoul National University, Seoul 08826, Republic of Korea.
authors.forename: Ju Yeon
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Epigenetics Institute, Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Lake
authors.affiliation: Department of Physics and Astronomy, Seoul National University, Seoul 08826, Republic of Korea.|Institute of Applied Physics, Seoul National University, Seoul 08826, Republic of Korea.|National Center of Creative Research Initiatives, Seoul National University, Seoul 08826, Republic of Korea.
authors.forename: Jaewon
authors.initials: J
authors.lastname: Kirk
authors.affiliation: Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
authors.forename: Vilhelm A
authors.initials: VA
authors.lastname: Bohr
authors.affiliation: Epigenetics Institute, Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Hua-Ying
authors.initials: HY
authors.lastname: Fan
authors.affiliation: Department of Physics and Astronomy, Seoul National University, Seoul 08826, Republic of Korea.|Institute of Applied Physics, Seoul National University, Seoul 08826, Republic of Korea.|National Center of Creative Research Initiatives, Seoul National University, Seoul 08826, Republic of Korea.
authors.forename: Sungchul
authors.initials: S
authors.lastname: Hohng
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D002843:Chromatin / Q000235:genetics; D042002:Chromatin Assembly and Disassembly / Q000235:genetics; D004265:DNA Helicases / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics*; D056488:Histone Chaperones / Q000235:genetics*; D006801:Humans; D056490:Nucleosome Assembly Protein 1 / Q000235:genetics*; D009707:Nucleosomes / Q000235:genetics; D000075223:Poly-ADP-Ribose Binding Proteins; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin; D056488:Histone Chaperones; C533557:NAP1L1 protein, human; D056490:Nucleosome Assembly Protein 1; D009707:Nucleosomes; D000075223:Poly-ADP-Ribose Binding Proteins; D000255:Adenosine Triphosphate; D004265:DNA Helicases; C078673:ERCC6 protein, human; D045643:DNA Repair Enzymes