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Review
. 2016 Jul 3;7(4):375-81.
doi: 10.1080/19491034.2016.1216743.

A role for Rtt109 in buffering gene-dosage imbalance during DNA replication

Affiliations
Review

A role for Rtt109 in buffering gene-dosage imbalance during DNA replication

Yoav Voichek et al. Nucleus. .

Abstract

Chromatin can function as an integrator of DNA-related processes, allowing communication, for example, between DNA replication and gene transcription. Such communication is needed to overcome the gene-dosage imbalance introduced during DNA replication, when certain genes are replicated prior to others. Increased transcription of early replicating genes could alter regulatory balances. This does not occur, suggesting a mechanism that suppresses expression from newly replicated DNA. Critical to this buffering is Rtt109, which acetylates the internal K56 residue of newly synthesized histone H3 prior to incorporation onto DNA. H3K56ac distinguishes replicated from non-replicated DNA, communicating this information to the transcription machinery to ensure expression homeostasis during S phase.

Keywords: Chromatin; DNA replication; H3K56ac; RTT109; gene expression.

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Figures

Figure 1.
Figure 1.
Histone modification as a means for communication and cross-regulation between different DNA regulated processes. (A) Histone modifications can serve as a platform for communication between the different DNA-dependent processes: DNA-related processes are coupled to changes in histone modifications and histone turnover. These include the eviction and assembly of histones during DNA replication and transcription, the modification of histones, in preparation and during these processes, and the recruitment of specific proteins (e.g. DNA repair machinery following DNA damage). We propose that through the platform of histone modifications, one process can pass information needed for the regulation of other DNA-dependent processes. (B) H3K56ac as a signal of communication between DNA replication and transcription: During replication, newly synthesized histones are acetylated by Rtt109 and Asf1 on H3K56. These histones are incorporated in replicated loci, allowing the discrimination between replicated and non-replicated regions. In turn, this information deposited by a replication-associated process, allows tuning expression to buffer changes in DNA dosage.

Comment on

  • doi: 10.1126/science.aad1162

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