DNA damage triggers nucleotide excision repair-dependent monoubiquitylation of histone H2A.
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.
Bergink
Steven
S
MGC Department of Cell Biology and Genetics, Center for Biomedical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands.
Salomons
Florian A
FA
Hoogstraten
Deborah
D
Groothuis
Tom A M
TA
de Waard
Harm
H
Wu
Junxin
J
Yuan
Li
L
Citterio
Elisabetta
E
Houtsmuller
Adriaan B
AB
Neefjes
Jacques
J
Hoeijmakers
Jan H J
JH
Vermeulen
Wim
W
Dantuma
Nico P
NP
D000595:Amino Acid Sequence; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D004247:DNA / Q000528:radiation effects; D004249:DNA Damage; D004260:DNA Repair; D006657:Histones / Q000378:metabolism*; D006801:Humans; D000071518:Liver X Receptors; D008969:Molecular Sequence Data; D057093:Orphan Nuclear Receptors; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism*; D043222:Ubiquitin Thiolesterase / Q000235:genetics / Q000378:metabolism*; D014466:Ultraviolet Rays
C400134:BAP1 protein, human; D018797:Cell Cycle Proteins; D006657:Histones; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D025521:Tumor Suppressor Proteins; D025801:Ubiquitin; D004247:DNA; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; D043222:Ubiquitin Thiolesterase; D046988:Proteasome Endopeptidase Complex