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GENES & DEVELOPMENT 20:1343-1352, 2006
©2006 by Cold Spring Harbor Laboratory Press; ISSN 0890-9369/ $5.00
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DNA damage triggers nucleotide excision repair-dependent monoubiquitylation of histone H2A

Steven Bergink1, Florian A. Salomons3, Deborah Hoogstraten1,3, Tom A.M. Groothuis5, Harm de Waard1, Junxin Wu3, Li Yuan3, Elisabetta Citterio4, Adriaan B. Houtsmuller2, Jacques Neefjes5, Jan H.J. Hoeijmakers1, Wim Vermeulen1,7 and Nico P. Dantuma3,6

1 MGC Department of Cell Biology and Genetics, Center for Biomedical Genetics 2 Department of Pathology, Erasmus Medical Center, Rotterdam 3015GE, The Netherlands; 3 Department of Cell and Molecular Biology, The Medical Nobel Institute, Karolinska Institutet, Stockholm S-17177, Sweden; 4 IFOM, Istituto FIRC di Oncologia Molecolare, Milan I-20139, Italy; 5 Division of Tumor Biology, The Netherlands Cancer Institute, Amsterdam 1066CX, The Netherlands

Chromatin changes within the context of DNA repair remain largely obscure. Here we show that DNA damage induces monoubiquitylation of histone H2A in the vicinity of DNA lesions. Ultraviolet (UV)-induced monoubiquitylation of H2A is dependent on functional nucleotide excision repair and occurs after incision of the damaged strand. The ubiquitin ligase Ring2 is required for the DNA damage-induced H2A ubiquitylation. UV-induced ubiquitylation of H2A is dependent on the DNA damage signaling kinase ATR (ATM- and Rad3-related) but not the related kinase ATM (ataxia telangiectasia-mutated). Although the response coincides with phosphorylation of variant histone H2AX, H2AX was not required for H2A ubiquitylation. Together our data show that monoubiquitylation of H2A forms part of the cellular response to UV damage and suggest a role of this modification in DNA repair-induced chromatin remodeling.

[Keywords: DNA repair; ubiquitin–proteasome system; histone; chromatin; ATR; H2AX; DNA damage response]

Received November 22, 2005; revised version accepted March 13, 2006.

6 Corresponding authors.

E-MAIL nico.dantuma{at}ki.se; FAX 46-8-313529.

7 E-MAIL w.vermeulen{at}erasmusmc.nl; FAX 31-10-4089468.

Supplemental material is available at http://www.genesdev.org.

Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.373706


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