The histone methyltransferase SET8 is required for S-phase progression

作者: Tobias Menzel , Morten Eskildsen , Ole Nørregaard Jensen , Thomas Helleday , Kristian Helin

DOI: 10.1083/JCB.200706150

关键词:

摘要: Chromatin structure and function is influenced by histone posttranslational modifications. SET8 (also known as PR-Set7 SETD8) a methyltransferase that monomethylates histonfe H4-K20. However, for in mammalian cell proliferation has not been determined. We show small interfering RNA inhibition of expression leads to decreased accumulation cells S phase. This accompanied DNA double-strand break (DSB) induction recruitment the repair proteins replication protein A, Rad51, 53BP1 damaged regions. depletion causes damage specifically during replication, which induces Chk1-mediated S-phase checkpoint. Furthermore, we find interacts with proliferating nuclear antigen through conserved motif, required fork progression. Finally, codepletion an important homologous recombination protein, abrogates after depletion. Overall, essential genomic stability results Chk1-dependent arrest.

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