ASH1L histone methyltransferase regulates the handoff between damage recognition factors in global-genome nucleotide excision repair

Global-genome nucleotide excision repair (GG-NER) prevents ultraviolet (UV) light-induced skin cancer by removing mutagenic cyclobutane pyrimidine dimers (CPDs). These lesions are formed abundantly on DNA wrapped around histone octamers in nucleosomes, but a specialized damage sensor known as DDB2 e...

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Vydáno v:Nature communications Ročník 8; číslo 1; s. 1333 - 13
Hlavní autoři: Balbo Pogliano, Chiara, Gatti, Marco, Rüthemann, Peter, Garajovà, Zuzana, Penengo, Lorenza, Naegeli, Hanspeter
Médium: Journal Article
Jazyk:angličtina
Vydáno: London Nature Publishing Group UK 06.11.2017
Nature Publishing Group
Nature Portfolio
Témata:
631/337/100/2285
631/337/1427/1430
631/45/147
631/80/458/1648
Chromatin
Cyclobutane
Cyclobutane pyrimidine dimers
Damage
Deoxyribonucleic acid
Dimers
DNA
DNA polymerase
Docking
Genomes
Histone H3
Histone methyltransferase
Humanities and Social Sciences
Hypersensitivity
Lesions
Lysine
multidisciplinary
Nucleosomes
Nucleotide excision repair
Proteins
Recognition
Repair
Science
Science (multidisciplinary)
Skin cancer
Ultraviolet radiation
XPC protein
ISSN:2041-1723, 2041-1723
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Shrnutí:Global-genome nucleotide excision repair (GG-NER) prevents ultraviolet (UV) light-induced skin cancer by removing mutagenic cyclobutane pyrimidine dimers (CPDs). These lesions are formed abundantly on DNA wrapped around histone octamers in nucleosomes, but a specialized damage sensor known as DDB2 ensures that they are accessed by the XPC initiator of GG-NER activity. We report that DDB2 promotes CPD excision by recruiting the histone methyltransferase ASH1L, which methylates lysine 4 of histone H3. In turn, methylated H3 facilitates the docking of the XPC complex to nucleosomal histone octamers. Consequently, DDB2, ASH1L and XPC proteins co-localize transiently on histone H3-methylated nucleosomes of UV-exposed cells. In the absence of ASH1L, the chromatin binding of XPC is impaired and its ability to recruit downstream GG-NER effectors diminished. Also, ASH1L depletion suppresses CPD excision and confers UV hypersensitivity. These findings show that ASH1L configures chromatin for the effective handoff between damage recognition factors during GG-NER activity. UV-induced mutagenic cyclobutane pyrimidine dimers on nucleosomal DNA are sensed by the damage recognition factors DDB2 and XPC via an unknown mechanism. Here, the authors show that the histone methyltransferase ASH1L regulates the DDB2 to XPC handoff by methylating Lys-4 of histone H3.
Bibliografie:ObjectType-Article-1
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ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-017-01080-8