Crosstalk between histone modifications during the DNA damage response

Attikum, Haico van; Gasser, Susan M.

doi:10.1016/j.tcb.2009.03.001

Cited by 467 publications

(399 citation statements)

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“…2C). Compatible with a model of interdependence between ␥-H2AX formation and MDC1 focus formation (27,28,42), cells overexpressing His-or GFP-TPX2 also displayed impaired formation of MDC1 ionizing radiation-induced foci (Fig. 2D).…”

Section: -H)mentioning

confidence: 52%

Targeting Protein for Xenopus Kinesin-like Protein 2 (TPX2) Regulates γ-Histone 2AX (γ-H2AX) Levels upon Ionizing Radiation

Neumayer

Helfricht

Shim

et al. 2012

Journal of Biological Chemistry

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Section: -H)mentioning

confidence: 52%

Targeting Protein for Xenopus Kinesin-like Protein 2 (TPX2) Regulates γ-Histone 2AX (γ-H2AX) Levels upon Ionizing Radiation

Neumayer

Helfricht

Shim

et al. 2012

Journal of Biological Chemistry

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“…The functions of chromatin remodeling complexes in transcription have been well established, and recent studies have also begun to reveal links between chromatin remodeling complexes and other nuclear events such as DNA repair and checkpoint regulation Morrison and Shen 2009;van Attikum and Gasser 2009). ATP-dependent chromatin remodeling complexes such as SWI/SNF have been shown to be involved in DNA repair and are also implicated in human cancer (Chai et al 2005;Wilson and Roberts 2011).…”

Section: Discussionmentioning

confidence: 99%

Regulation of Mec1 kinase activity by the SWI/SNF chromatin remodeling complex

et al. 2015

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ATP-dependent chromatin remodeling complexes alter chromatin structure through interactions with chromatin substrates such as DNA, histones, and nucleosomes. However, whether chromatin remodeling complexes have the ability to regulate nonchromatin substrates remains unclear. Saccharomyces cerevisiae checkpoint kinase Mec1 (ATR in mammals) is an essential master regulator of genomic integrity. Here we found that the SWI/SNF chromatin remodeling complex is capable of regulating Mec1 kinase activity. In vivo, Mec1 activity is reduced by the deletion of Snf2, the core ATPase subunit of the SWI/SNF complex. SWI/SNF interacts with Mec1, and cross-linking studies revealed that the Snf2 ATPase is the main interaction partner for Mec1. In vitro, SWI/SNF can activate Mec1 kinase activity in the absence of chromatin or known activators such as Dpb11. The subunit requirement of SWI/SNFmediated Mec1 regulation differs from that of SWI/SNF-mediated chromatin remodeling. Functionally, SWI/SNFmediated Mec1 regulation specifically occurs in S phase of the cell cycle. Together, these findings identify a novel regulator of Mec1 kinase activity and suggest that ATP-dependent chromatin remodeling complexes can regulate nonchromatin substrates such as a checkpoint kinase.

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“…DNA repair is no exception, and dynamic changes in chromatin condensation and accompanying histone marks have been recognized as inevitable DDR pathways [15,[75][76][77][78][79][80]. Here, too, the DDR relies on recruitment of existing players in the chromatin organization arena [32][33][34][75][76][77][78][79][81][82][83][84][85].…”

Section: Rnf20-rnf40 Is Called To Emergency Action Upon Dna Damage Inmentioning

confidence: 99%

“…Information about the interface between the DDR and chromatin organization is rapidly accumulating [75,76,78,108,[118][119][120]]. An early, extremely rapid process at damage sites is the CK2-mediated phosphorylation and eviction of the heterochromatin protein 1 (HP1) [121].…”

Section: Rnf20-rnf40 Is Called To Emergency Action Upon Dna Damage Inmentioning

confidence: 99%

“…Thus, the two histone monoubiquitylations may play opposing roles in the dynamics of chromatin organization: H2Bub in the immediate vicinity of DSBs, and H2Aub farther away from these lesions. Indeed, despite the apparent analogy between the two modifications, H2Aub, at the opposing side of the nucleosomal surface, does not lead to chromatin fiber decompaction [70].Information about the interface between the DDR and chromatin organization is rapidly accumulating [75,76,78,108,[118][119][120]]. An early, extremely rapid process at damage sites is the CK2-mediated phosphorylation and eviction of the heterochromatin protein 1 (HP1) [121].…”

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RNF20–RNF40: A ubiquitin‐driven link between gene expression and the DNA damage response

et al. 2011

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a b s t r a c tThe DNA damage response (DDR) is emerging as a vast signaling network that temporarily modulates numerous aspects of cellular metabolism in the face of DNA lesions, especially critical ones such as the double strand break (DSB). The DDR involves extensive dynamics of protein post-translational modifications, most notably phosphorylation and ubiquitylation. The DSB response is mobilized primarily by the ATM protein kinase, which phosphorylates a plethora of key players in its various branches. It is based on a core of proteins dedicated to the damage response, and a cadre of proteins borrowed temporarily from other cellular processes to help meet the challenge. A recently identified novel component of the DDR pathway -histone H2B monoubiquitylationexemplifies this principle. In mammalian cells, H2B monoubiquitylation is driven primarily by an E3 ubiquitin ligase composed of the two RING finger proteins RNF20 and RNF40. Generation of monoubiquitylated histone H2B (H2Bub) has been known to be coupled to gene transcription, presumably modulating chromatin decondensation at transcribed regions. New evidence indicates that the regulatory function of H2Bub on gene expression can selectively enhance or suppress the expression of distinct subsets of genes through a mechanism involving the hPAF1 complex and the TFIIS protein. This delicate regulatory process specifically affects genes that control cell growth and genome stability, and places RNF20 and RNF40 in the realm of tumor suppressor proteins. In parallel, it was found that following DSB induction, the H2B monoubiquitylation module is recruited to damage sites where it induces local H2Bub, which in turn is required for timely recruitment of DSB repair protein and, subsequently, timely DSB repair. This pathway represents a crossroads of the DDR and chromatin organization, and is a typical example of how the DDR calls to action functional modules that in unprovoked cells regulate other processes. Ó 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. The DNA damage response: borrowing functional modules in an emergencyCellular metabolism is controlled by numerous, interlocked signaling networks. These networks are constantly responding to internal and external stimuli related to the cell's normal life cycle and functions, and to threats to its well being. A major threat to cellular homeostasis is subversion of its genomic stability, which may lead to undue cell death or to neoplasia [1,2]. DNA damage caused by internal or external damaging agents is a major danger to the integrity of the cellular genome. The cellular defense system against this threat is the DNA damage response (DDR) -an elaborate signaling network activated by DNA damage, which swiftly modulates many physiological processes [3,4]. A strong trigger of the DDR is the DNA double-strand break (DSB) [5,6]. DSBs are induced by ionizing radiation, radiomimetic chemicals, reactive oxygen species formed in the course of normal metabolism, and can also result from replic...

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Crosstalk between histone modifications during the DNA damage response

Cited by 467 publications

References 87 publications

Targeting Protein for Xenopus Kinesin-like Protein 2 (TPX2) Regulates γ-Histone 2AX (γ-H2AX) Levels upon Ionizing Radiation

Targeting Protein for Xenopus Kinesin-like Protein 2 (TPX2) Regulates γ-Histone 2AX (γ-H2AX) Levels upon Ionizing Radiation

Regulation of Mec1 kinase activity by the SWI/SNF chromatin remodeling complex

RNF20–RNF40: A ubiquitin‐driven link between gene expression and the DNA damage response

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