The poly(ADP-ribose)-dependent chromatin remodeler Alc1 induces local chromatin relaxation upon DNA damage

Sellou, Hafida; Lebeaupin, Théo; Chapuis, Catherine; Smith, Rebecca; Hegele, Anna; Singh, Hari; Kozłowski, Marek; Bultmann, Sebastian; Ladurner, Andreas G.; Timinszky, Gyula; Huet, Sébastien

doi:10.1091/mbc.e16-05-0269

Cited by 113 publications

(141 citation statements)

References 40 publications

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“…Furthermore, PARP-1 was required for MRE-11 accumulation at DSBs because MRE-11 enrichment decreased significantly after treatment with DPQ. Consistent with our findings, studies show that chromatin relaxation at DNA damage sites is regulated by PARP-1 enzymatic activity (36,37), followed by DNA end resection, which involves MRE-11 endonuclease activity.…”

Section: Discussionsupporting

confidence: 92%

Poly(ADP‐ribose) polymerase‐1 promotes recruitment of meiotic recombination‐11 to chromatin and DNA double‐strand break repair in Ku70‐deficient breast cancer cells

et al. 2018

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Poly(ADP-ribose) polymerase (PARP)-1 may act in an error-prone pathway called alternative end joining (Alt-EJ) for DNA double-strand break (DSB) repair when nonhomologous end joining is defective. We examined the recruitment of PARP-1 to chromatin in response to radiomimetic agents and the effects of PARP-1 inhibition on DSB repair and recruitment of the meiotic recombination (MRE)-11-double-strand break repair (RAD50) protein-Nijmegen breakage syndrome (NSB)-1 (MRN) complex to the chromatin in Ku70-deficient breast cancer cells. The chromatin-binding affinity of PARP-1 was enhanced in response to neocarzinostatin (NCS) or calicheamicin treatment in the absence of Ku70. PARP-1 inhibition impaired the repair of both NCS-induced DSBs and intron-encoded endonuclease from Physarum polycephalum-induced site-specific DSB. Both fractionation and chromatin immunoprecipitation assays demonstrated that chromatin recruitment of MRN was PARP-1 dependent. These data suggest that PARP-1 is vital for DSB repair in breast cancer cells when Alt-EJ is activated.-Huang, Y., Shao, Q., Luo, X., Yang, D., Zeng, B., Xiang, T., Ren, G., Cheng, Q. Poly(ADP-ribose) polymerase-1 promotes recruitment of meiotic recombination-11 to chromatin and DNA double-strand break repair in Ku70-deficient breast cancer cells.

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Section: Discussionsupporting

confidence: 92%

Poly(ADP‐ribose) polymerase‐1 promotes recruitment of meiotic recombination‐11 to chromatin and DNA double‐strand break repair in Ku70‐deficient breast cancer cells

et al. 2018

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“…Our data support this proposed mode of recruitment given that: (1) 53BP1 strongly parallels the pattern observed with γH2AX and the FK2 antibody (although the broad specificity of this antibody toward many ubiquitinated substrates precludes a definitive conclusion regarding the nature of the modified protein) and (2) 53BP1 association with DSB is minimal in G2, in agreement with the proposed dilution of H4K20me2 on post-replicative chromatin (Pellegrino et al., 2017). H1, on the other hand, was recently shown to be displaced from sites of DNA damage (Sellou et al., 2016, Strickfaden et al., 2016). Interestingly, RNF8-mediated H1 ubiquitination loosens its interaction with chromatin (Thorslund et al., 2015), providing potential mechanisms for H1 eviction from megabase-wide γH2AX domains.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Mapping of Histone Modifications at DNA Double-Strand Breaks Deciphers Repair Pathway Chromatin Signatures

et al. 2018

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SummaryDouble-strand breaks (DSBs) are extremely detrimental DNA lesions that can lead to cancer-driving mutations and translocations. Non-homologous end joining (NHEJ) and homologous recombination (HR) represent the two main repair pathways operating in the context of chromatin to ensure genome stability. Despite extensive efforts, our knowledge of DSB-induced chromatin still remains fragmented. Here, we describe the distribution of 20 chromatin features at multiple DSBs spread throughout the human genome using ChIP-seq. We provide the most comprehensive picture of the chromatin landscape set up at DSBs and identify NHEJ- and HR-specific chromatin events. This study revealed the existence of a DSB-induced monoubiquitination-to-acetylation switch on histone H2B lysine 120, likely mediated by the SAGA complex, as well as higher-order signaling at HR-repaired DSBs whereby histone H1 is evicted while ubiquitin and 53BP1 accumulate over the entire γH2AX domains.

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“…All human cells (listed in table 1) were cultured at 37°C in an atmosphere of 5% CO2 in DMEM (Thermo Fisher Scientific) supplemented with penicillin/streptomycin (Sigma) and 10% Fetal bovine serum (FBS; Bodinco BV). Parental U2OS (WT) cells were a gift from Andreas Ladurner 35 . Plasmid constructs.…”

Section: Methodsmentioning

confidence: 99%

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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The poly(ADP-ribose)-dependent chromatin remodeler Alc1 induces local chromatin relaxation upon DNA damage

Abstract: PARP1 and its effector, the ATP-dependent chromatin remodeler Alc1/Chd1L, are identified as key players during the rapid chromatin relaxation at DNA damage sites.

Cited by 113 publications

References 40 publications

Poly(ADP‐ribose) polymerase‐1 promotes recruitment of meiotic recombination‐11 to chromatin and DNA double‐strand break repair in Ku70‐deficient breast cancer cells

Poly(ADP‐ribose) polymerase‐1 promotes recruitment of meiotic recombination‐11 to chromatin and DNA double‐strand break repair in Ku70‐deficient breast cancer cells

Comprehensive Mapping of Histone Modifications at DNA Double-Strand Breaks Deciphers Repair Pathway Chromatin Signatures

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

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