title: DDB2 promotes chromatin decondensation at UV-induced DNA damage.
abstract: Nucleotide excision repair (NER) is the principal pathway that removes helix-distorting deoxyribonucleic acid (DNA) damage from the mammalian genome. Recognition of DNA lesions by xeroderma pigmentosum group C (XPC) protein in chromatin is stimulated by the damaged DNA-binding protein 2 (DDB2), which is part of a CUL4A-RING ubiquitin ligase (CRL4) complex. In this paper, we report a new function of DDB2 in modulating chromatin structure at DNA lesions. We show that DDB2 elicits unfolding of large-scale chromatin structure independently of the CRL4 ubiquitin ligase complex. Our data reveal a marked adenosine triphosphate (ATP)-dependent reduction in the density of core histones in chromatin containing UV-induced DNA lesions, which strictly required functional DDB2 and involved the activity of poly(adenosine diphosphate [ADP]-ribose) polymerase 1. Finally, we show that lesion recognition by XPC, but not DDB2, was strongly reduced in ATP-depleted cells and was regulated by the steady-state levels of poly(ADP-ribose) chains.
authors.affiliation: Department of Cell and Molecular Biology, Karolinska Institutet, S-17177 Stockholm, Sweden. MartijnLuijsterburg@lumc.nl
authors.forename: Martijn S
authors.initials: MS
authors.lastname: Luijsterburg
authors.forename: Michael
authors.initials: M
authors.lastname: Lindh
authors.forename: Klara
authors.initials: K
authors.lastname: Acs
authors.forename: Mischa G
authors.initials: MG
authors.lastname: Vrouwe
authors.forename: Alex
authors.initials: A
authors.lastname: Pines
authors.forename: Haico
authors.initials: H
authors.lastname: van Attikum
authors.forename: Leon H
authors.initials: LH
authors.lastname: Mullenders
authors.forename: Nico P
authors.initials: NP
authors.lastname: Dantuma
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism*; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006801:Humans; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism; D058767:Protein Unfolding; D034622:RNA Interference; D034741:RNA, Small Interfering; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D002843:Chromatin; C117669:DDB2 protein, human; D004268:DNA-Binding Proteins; D006657:Histones; D034741:RNA, Small Interfering; C086984:XPC protein, human; D000255:Adenosine Triphosphate; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases