Set2 methyltransferase facilitates DNA replication and promotes genotoxic stress responses through MBF-dependent transcription

Pai, Chen-Chun, Kishkevich, Anastasiya, Deegan, Rachel S, Keszthelyi, Andrea, Folkes, Lisa, Kearsey, Stephen E, De León, Nagore, Soriano, Ignacio, de Bruin, Robertus Antonius Maria, Carr, Antony M and Humphrey, Timothy C (2017) Set2 methyltransferase facilitates DNA replication and promotes genotoxic stress responses through MBF-dependent transcription. Cell Reports, 20 (11). pp. 2693-2705. ISSN 2211-1247

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Abstract

Chromatin modification through histone H3 lysine 36 methylation by the SETD2 tumour suppressor plays a key role in maintaining genome stability. Here we describe a role for Set2-dependent H3K36 methylation in facilitating DNA replication and the transcriptional responses to both replication stress and DNA damage through promoting MluI Cell Cycle Box (MCB) binding factor (MBF) complex-dependent transcription in fission yeast. Set2 loss leads to reduced MBF-dependent ribonucleotide reductase (RNR) expression, reduced deoxyribonucleoside triphosphate (dNTP) synthesis, altered replication origin firing and to a checkpoint-dependent S-phase delay. Accordingly, prolonged S-phase in the absence of Set2 is suppressed by increasing dNTP synthesis. Further, H3K36 is di- and tri-methylated at these
MBF gene promoters, and Set2 loss leads to reduced MBF binding and transcription in response to genotoxic stress. Together, these findings provide new insights into how H3K36 methylation facilitates DNA replication and promotes genotoxic stress responses in fission yeast.

Item Type: Article
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
Research Centres and Groups: Genome Damage and Stability Centre
Subjects: Q Science > Q Science (General)
Depositing User: Sarah Frances
Date Deposited: 22 Sep 2017 11:46
Last Modified: 28 Sep 2017 07:59
URI: http://sro.sussex.ac.uk/id/eprint/70315

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Project NameSussex Project NumberFunderFunder Ref
Single Molecule Imaging of the DNA Damage Response in Live CellsG0250EUROPEAN UNION268788