Histone acetylation by HBO1 tightens replication licensing

Abstract

In this issue of Molecular Cell, Miotto and Struhl (2010) suggest that replication licensing, the loading of Mcm2-7 onto DNA, is promoted by HBO1 acetylating histone H4 at replication origins, providing a molecular view of how chromatin status influences origin usage.

Figure 1. Regulation of replication licensing by Hbo1

(A) From late M- to G1-phase ORC, Cdc6 and Cdt1 sequentially load onto chromatin to mark origins of replication. (B) Cdt1-assisted binding of Hbo1 to origins results in acetylation of histone H4 at origins. (C) The presence of ORC-Cdc6-Cdt1 and acetylated histones facilitate the loading of Mcm2-7 complex. (D) Geminin binds to Cdt1 during S- and G2-phases of cell cycle and blocks its interaction with Mcm2-7 as well as inhibiting Hbo1 mediated H4 acetylation thus preventing re-loading of Mcm2-7 once replication is initiated.