This work shows that the replacement of histones is coordinated with the fork progression during DNA replication. After finding that Asf1, the H3-H4 chaperone, co- purified with the putative helicase MCM2-7 in HeLa cells, the question then was if problems during replication could be the consequence of abnormal chromatin unwinding. This was confirmed by following the cell cycle progression with DNA binding markers and by silencing of Asf1 with siRNAs. Formation of ssDNA was also reduced after Asf1 depletion, i.e., [indicating...] that impaired replication reflects a DNA unwinding defect and implied that DNA in chromatin cannot be properly unwound by the replicative helicase. This could reflect a direct effect of Asf1 on DNA unwinding and fork progression or indirect effects, involving DNA damage at the replication fork, replisome collapse, and/or checkpoint signaling. [...] Our results show that replication fork progression is dependent on the histone H3-H4 chaperone, Asf1, and on an equilibrium between histone supply and demand. This dependency could ensure that replication only proceeds when nucleosomes are being formed behind the fork with a proper balance between new and parental histones H3-H4Groth A., et al. 2007. Science 318(5858):1928-1931
epigenetics
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