Real-Time Tracking of Parental Histones Reveals Their Contribution to Chromatin Integrity Following DNA Damage

Adam, Salomé; Dabin, Juliette; Chevallier, Odile; Leroy, Olivier; Baldeyron, Céline; Corpet, Armelle; Lomonte, Patrick; Renaud, Olivier; Almouzni, Geneviève; Polo, Sophie E.

doi:10.1016/j.molcel.2016.08.019

Cited by 54 publications

(61 citation statements)

References 56 publications

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“…The remaining single-stranded gap is filled by DNA synthesis and closed by DNA ligation (Moser et al, 2007;Ogi et al, 2010). To allow for repair despite compaction of the DNA substrate in chromatin, this multi-step process involves the temporary release of histones from damaged DNA (Adam et al, 2016) but how these chromatin rearrangements take place is not yet understood.…”

Section: Introductionmentioning

confidence: 99%

Chromatin remodeler CHD1 promotes XPC‐to‐TFIIH handover of nucleosomal UV lesions in nucleotide excision repair

et al. 2017

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Ultraviolet (UV) light induces mutagenic cyclobutane pyrimidine dimers (CPDs) in nucleosomal DNA that is tightly wrapped around histone octamers. How global-genome nucleotide excision repair (GG-NER) processes CPDs despite that this chromatin arrangement is poorly understood. An increased chromatin association of CHD1 (chromodomain helicase DNA-binding 1) upon UV irradiation indicated possible roles of this chromatin remodeler in the UV damage response. Immunoprecipitation of chromatin fragments revealed that CHD1 co-localizes in part with GG-NER factors. Chromatin fractionation showed that the UV-dependent recruitment of CHD1 occurs to UV lesions in histone-assembled nucleosomal DNA and that this CHD1 relocation requires the lesion sensor XPC (xeroderma pigmentosum group C). immunofluorescence analyses further demonstrate that CHD1 facilitates substrate handover from XPC to the downstream TFIIH (transcription factor IIH). Consequently, CHD1 depletion slows down CPD excision and sensitizes cells to UV-induced cytotoxicity. The finding of a CHD1-driven lesion handover between sequentially acting GG-NER factors on nucleosomal histone octamers suggests that chromatin provides a recognition scaffold enabling the detection of a subset of CPDs.

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Section: Introductionmentioning

confidence: 99%

Chromatin remodeler CHD1 promotes XPC‐to‐TFIIH handover of nucleosomal UV lesions in nucleotide excision repair

et al. 2017

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“…We propose that human cells may not have a need for HMGN1-mediated chromatin modulation to remove CPDs during TCR, because these lesions are targeted by DDB2-mediated GGR. Indeed, several studies have revealed that DDB2 mediates higher-order chromatin unfolding at sites of UV-induced DNA damage 33,34 similar to what has been proposed for HMGN1 in mouse cells 15 .…”

Section: The Strong Evolutionary Similarity (83%) Between Human and Mmentioning

confidence: 52%

Human HMGN1 and HMGN2 are not required for transcription-coupled DNA repair

Apelt

Zoutendijk

Gout

et al. 2019

Preprint

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Running title: HMGN1 is not involved in TCR * Corresponding author: Martijn Luijsterburg (m.luijsterburg@lumc.nl) 2 Apelt et al. Human HMGN1 and HMGN2 are not required for TCR SummaryTranscription-coupled repair (TCR) removes DNA lesions from the transcribed strand of active genes. Stalling of RNA polymerase II (RNAPII) at DNA lesions initiates TCR through the recruitment of the CSB and CSA proteins. The full repertoire of proteins required for human TCR -particularly in a chromatin context -remains to be determined. Studies in mice have revealed that the nucleosome-binding protein HMGN1 is required to enhance the repair of UV-induced lesions in transcribed genes.However, whether HMGN1 is required for human TCR remains unaddressed. Here, we show that knockout or knockdown of HMGN1, either alone or in combination with HMGN2, does not render human cells sensitive to UV light or Illudin S-induced transcription-blocking DNA lesions. Moreover, transcription restart after UV irradiation was not impaired in HMGN-deficient cells. In contrast, TCR-deficient cells were highly sensitive to DNA damage and failed to restart transcription. Furthermore, GFP-tagged HMGN1 was not recruited to sites of UV-induced DNA damage under conditions were GFP-CSB readily accumulated. In line with this, HMGN1 did not associate with the TCR complex, nor did TCR proteins require HMGN1 to associate with DNA damagestalled RNAPII. Together, our findings suggest that HMGN1 and HMGN2 are not required for human TCR.

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“…We have shown that ANP32E increases cell survival to UVC irradiation, suggesting that ANP32E-mediated removal of H2A.Z from UVC-damaged chromatin may be of functional importance. Given that H2A.Z promotes chromatin folding in vitro (Fan et al, 2002;, the local depletion of H2A.Z could contribute to the chromatin relaxation observed at UVC damage sites (Adam et al, 2016;Luijsterburg et al, 2012). In line with this hypothesis, H2A.Z removal by ANP32E is required for histone H4 acetylation at sites of DNA doublestrand breaks (Gursoy-Yuzugullu et al, 2015).…”

Section: H2az/h2ax Exchange At Sites Of Dna Damage Repairmentioning

confidence: 84%

The histone chaperone FACT coordinates H2A.X-dependent signaling and repair of DNA damage

Piquet

Parc

Bai

et al. 2018

Preprint

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SUMMARYSafeguarding cell function and identity following a genotoxic stress challenge entails a tight coordination of DNA damage signaling and repair with chromatin maintenance. How this coordination is achieved and with what impact on chromatin integrity remains elusive. Here, by investigating the mechanisms governing the distribution of H2A.X in mammalian chromatin, we demonstrate that this histone variant is deposited de novo at sites of DNA damage in a repair synthesis-coupled manner. Our mechanistic studies further identify the histone chaperone FACT (Facilitates Chromatin Transcription) as responsible for the deposition of newly synthesized H2A.X. Functionally, FACT potentiates H2A.X-dependent signaling of DNA damage and, together with ANP32E (Acidic Nuclear Phosphoprotein 32 Family Member E), orchestrates a H2A.Z/H2A.X exchange reaction that reshapes the chromatin landscape at repair sites. We propose that this mechanism promotes chromatin accessibility and helps tailoring DNA damage signaling to repair progression.HIGHLIGHTSH2A.X, but not H2A.Z, is deposited de novo at sites of DNA damage repairFACT promotes new H2A.X deposition coupled to repair synthesisFACT and ANP32E chaperones orchestrate H2A.Z/H2A.X exchange in damaged chromatinFACT stimulates H2A.X-dependent signaling of DNA damage

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Real-Time Tracking of Parental Histones Reveals Their Contribution to Chromatin Integrity Following DNA Damage

Cited by 54 publications

References 56 publications

Chromatin remodeler CHD1 promotes XPC‐to‐TFIIH handover of nucleosomal UV lesions in nucleotide excision repair

Chromatin remodeler CHD1 promotes XPC‐to‐TFIIH handover of nucleosomal UV lesions in nucleotide excision repair

Human HMGN1 and HMGN2 are not required for transcription-coupled DNA repair

The histone chaperone FACT coordinates H2A.X-dependent signaling and repair of DNA damage

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