Investigation of H2<scp>AX</scp> methylation by the <scp>SUV</scp>39H2 protein lysine methyltransferase

Schuhmacher, Maren Kirstin; Kudithipudi, Srikanth; Jeltsch, Albert

doi:10.1002/1873-3468.12216

Cited by 9 publications

(11 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Acetylation of K5 by TIP60 does not only facilitate ubiquitination at K119 and mobility [ 76 , 77 ], it is also required for the accumulation of the repair factor NBS1 and Poly-ADP-ribosyl-polymerase 1 (PARP1/ARTD1) activity [ 132 , 133 ]. Methylation of K134 is involved in the repair process and contributes to the recruitment of the kinases ATM and ATR [ 79 ], but the function of Suv39H2 as K134 methylase is highly controversial [ 80 ]. Another acetylation catalysed by CBP/p300 on K36 is independent of DNA damage, but might contribute to survival signalling [ 78 ].…”

Section: Features and Post-translational Modifications Of H2az Hmentioning

confidence: 99%

Post-Translational Modifications of H2A Histone Variants and Their Role in Cancer

Corujo

Buschbeck

2018

Cancers

View full text Add to dashboard Cite

Histone variants are chromatin components that replace replication-coupled histones in a fraction of nucleosomes and confer particular characteristics to chromatin. H2A variants represent the most numerous and diverse group among histone protein families. In the nucleosomal structure, H2A-H2B dimers can be removed and exchanged more easily than the stable H3-H4 core. The unstructured N-terminal histone tails of all histones, but also the C-terminal tails of H2A histones protrude out of the compact structure of the nucleosome core. These accessible tails are the preferential target sites for a large number of post-translational modifications (PTMs). While some PTMs are shared between replication-coupled H2A and H2A variants, many modifications are limited to a specific histone variant. The present review focuses on the H2A variants H2A.Z, H2A.X, and macroH2A, and summarizes their functions in chromatin and how these are linked to cancer development and progression. H2A.Z primarily acts as an oncogene and macroH2A and H2A.X as tumour suppressors. We further focus on the regulation by PTMs, which helps to understand a degree of context dependency.

show abstract

Section: Features and Post-translational Modifications Of H2az Hmentioning

confidence: 99%

Post-Translational Modifications of H2A Histone Variants and Their Role in Cancer

Corujo

Buschbeck

2018

Cancers

View full text Add to dashboard Cite

show abstract

“…To give another example, the H3K9 PKMT SUV39H2 was reported to methylate K134 of H2AX, and thus stimulate H2AX phosphorylation during DNA damage response (Sone et al, 2014). However, the amino acid sequence context of the H2AX methylation site does not fit to the specificity profile of SUV39H2 (Schuhmacher et al, 2015) and the methylation could not be validated in followup biochemical work (Schuhmacher et al, 2016).…”

Section: Examples Of Pkmt Substrates That Did Not Stand the Test Of Timementioning

confidence: 99%

Approaches and Guidelines for the Identification of Novel Substrates of Protein Lysine Methyltransferases

Kudithipudi

Jeltsch

2016

Cell Chemical Biology

Self Cite

View full text Add to dashboard Cite

Protein lysine methylation is emerging as a general post-translational modification (PTM) with essential functions regulating protein stability, activity, and protein-protein interactions. One of the outstanding challenges in this field is linking protein lysine methyltransferases (PKMTs) with specific substrates and lysine methylation events in a systematic manner. Inability to validate reported PKMT substrates delayed progress in the field and cast unnecessary doubt about protein lysine methylation as a truly general PTM. Here, we aim to provide a concise guide to help avoid some of the most common pitfalls in studies searching for new PKMT substrates and propose a set of seven basic biochemical rules: (1) include positive controls; (2) use target lysine mutations of substrate proteins as negative controls; (3) use inactive enzyme variants as negative controls; (4) report quantitative methylation data; (5) consider PKMT specificity; (6) validate methyl lysine antibodies; and (7) connect cellular and in vitro results. We explain the logic behind them and discuss how they should be implemented in the experimental work.

show abstract

“…However, the sequence context of H2AX-K134 does not fit with the specificity of SUV39H2, which generally methylates H3K9. In a subsequent study, in vitro methylation reaction assays with SUV39H2 (and its homolog SUV39H1), using H2AX protein and peptides, did not produce any methylation at K134 or any other lysine (Schuhmacher et al, 2016). Nonetheless, these data cannot rule out H2AX methylation by SUV39H2 in cells.…”

Section: Lysine Methylation In Histone H2ax Tailmentioning

confidence: 88%

The Role of Histone Lysine Methylation in the Response of Mammalian Cells to Ionizing Radiation

et al. 2021

View full text Add to dashboard Cite

Eukaryotic genomes are wrapped around nucleosomes and organized into different levels of chromatin structure. Chromatin organization has a crucial role in regulating all cellular processes involving DNA-protein interactions, such as DNA transcription, replication, recombination and repair. Histone post-translational modifications (HPTMs) have a prominent role in chromatin regulation, acting as a sophisticated molecular code, which is interpreted by HPTM-specific effectors. Here, we review the role of histone lysine methylation changes in regulating the response to radiation-induced genotoxic damage in mammalian cells. We also discuss the role of histone methyltransferases (HMTs) and histone demethylases (HDMs) and the effects of the modulation of their expression and/or the pharmacological inhibition of their activity on the radio-sensitivity of different cell lines. Finally, we provide a bioinformatic analysis of published datasets showing how the mRNA levels of known HMTs and HDMs are modulated in different cell lines by exposure to different irradiation conditions.

show abstract

Investigation of H2AX methylation by the SUV39H2 protein lysine methyltransferase

Cited by 9 publications

References 30 publications

Post-Translational Modifications of H2A Histone Variants and Their Role in Cancer

Post-Translational Modifications of H2A Histone Variants and Their Role in Cancer

Approaches and Guidelines for the Identification of Novel Substrates of Protein Lysine Methyltransferases

The Role of Histone Lysine Methylation in the Response of Mammalian Cells to Ionizing Radiation

Contact Info

Product

Resources

About