Histone H2B ubiquitylation disrupts local and higher-order chromatin compaction

Fierz, Beat; Chatterjee, Champak; McGinty, Robert K.; Bar-Dagan, Maya; Raleigh, Daniel P.; Muir, Tom W.

doi:10.1038/nchembio.501

Cited by 401 publications

(411 citation statements)

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

confidence: 75%

“…Loss of histone H2B at DSB sites was previously reported in the budding yeast [124], and shown to be ATM-dependent and required for XRCC4 recruitment in human cells [125]. Such displacement may follow the decompaction of the chromatin fiber caused by H2Bub [70].A. Nussenzweig's laboratory previously showed an initial, very rapid chromatin relaxation at DSB sites that was ATP-dependent and ATM-independent, and was required for the recruitment of the damage sensors [126,127].…”

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confidence: 84%

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

confidence: 97%

“…1). It is also plausible that H2Bub alters chromatin structure in the specific context of those genes and makes it more accessible to the transcription machinery [70]. Alternatively, RNF20 may affect the activity of some transcriptional regulators, especially since it was shown to directly bind and influence the transcriptional activity of the transcription factor and tumor suppressor protein p53 [55].…”

mentioning

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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confidence: 99%

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

confidence: 75%