ATAD2 is an epigenetic reader of newly synthesized histone marks during DNA replication
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Author
Koo, Seong Joo
Fernández-Montalván, Amaury E.
Badock, Volker
Holton, Simon J.
von Ahsen, Oliver
Toedling, Joern
Vittori, Sarah
Gorjánácz, Mátyás
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https://doi.org/10.18632/oncotarget.11855Metadata
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Koo, Seong Joo, Amaury E. Fernández-Montalván, Volker Badock, Christopher J. Ott, Simon J. Holton, Oliver von Ahsen, Joern Toedling, Sarah Vittori, James E. Bradner, and Mátyás Gorjánácz. 2016. “ATAD2 is an epigenetic reader of newly synthesized histone marks during DNA replication.” Oncotarget 7 (43): 70323-70335. doi:10.18632/oncotarget.11855. http://dx.doi.org/10.18632/oncotarget.11855.Abstract
ATAD2 (ATPase family AAA domain-containing protein 2) is a chromatin regulator harboring an AAA+ ATPase domain and a bromodomain, previously proposed to function as an oncogenic transcription co-factor. Here we suggest that ATAD2 is also required for DNA replication. ATAD2 is co-expressed with genes involved in DNA replication in various cancer types and predominantly expressed in S phase cells where it localized on nascent chromatin (replication sites). Our extensive biochemical and cellular analyses revealed that ATAD2 is recruited to replication sites through a direct interaction with di-acetylated histone H4 at K5 and K12, indicative of newly synthesized histones during replication-coupled chromatin reassembly. Similar to ATAD2-depletion, ectopic expression of ATAD2 mutants that are deficient in binding to these di-acetylation marks resulted in reduced DNA replication and impaired loading of PCNA onto chromatin, suggesting relevance of ATAD2 in DNA replication. Taken together, our data show a novel function of ATAD2 in cancer and for the first time identify a reader of newly synthesized histone di-acetylation-marks during replication.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5342555/pdf/Terms of Use
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