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HBO1 Histone Acetylase Activity Is Essential for DNA Replication Licensing and Inhibited by Geminin
Open accessAbstract
HBO1, an H4-specific histone acetylase, is a co-activator of the DNA replication licensing factor Cdt1. HBO1 acetylase activity is required for licensing, because a HAT-defective mutant of HBO1 bound at origins is unable to load the MCM complex. H4 acetylation at origins is cell-cycle regulated, with maximal activity at the G1/S transition, and co-expression of HBO1 and Jade1 increases histone acetylation and MCM complex loading. Overexpression of the Set8 histone H4 tail-binding domain specifically inhibits MCM loading, suggesting that histones are a physiologically relevant target for licensing. Lastly, Geminin, inhibits HBO1 acetylase activity in the context of a Cdt1-HBO1 complex, and it associates with origins and inhibits H4 acetylation and licensing in vivo. Thus, H4 acetylation at origins by HBO1 is critical for replication licensing by Cdt1, and negative regulation of licensing by Geminin is likely to involve inhibition of HBO1 histone acetylase activity.
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Metadata
- Authors
- Miotto, B., & Struhl, K.
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2010-01
- Volume
- 37
- Issue
- 1
- Pages
- 57-66
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W2074637369
- Cited by
- 258
- References
- 0
- FWCI
- 9.69
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Miotto, B., & Struhl, K. (2010). HBO1 Histone Acetylase Activity Is Essential for DNA Replication Licensing and Inhibited by Geminin. Molecular Cell. https://doi.org/10.1016/j.molcel.2009.12.012
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