Transcription Recovery after DNA Damage Requires Chromatin Priming by the H3.3 Histone Chaperone HIRA

Adam, Salomé; Polo, Sophie E.; Almouzni, Geneviève

doi:10.1016/j.cell.2013.08.029

Cited by 254 publications

(242 citation statements)

References 71 publications

Supporting

Mentioning

228

Contrasting

Order By: Relevance

“…Therefore, both the K85R mutation (which could not stabilize chromatin organization as WT H1) and the K85Q mutation (which failed to relax chromatin fibers) can lead to impaired cell survival in response to DNA damage. Our results are further supported by the theory that failure to establish an accessible chromatin environment or to restore chromatin compaction leads to defective chromatin functions, such as transcription (47,48). …”

Section: Discussionsupporting

confidence: 80%

Histone H1 acetylation at lysine 85 regulates chromatin condensation and genome stability upon DNA damage

Dong

et al. 2018

Nucleic Acids Research

View full text Add to dashboard Cite

Linker histone H1 has a key role in maintaining higher order chromatin structure and genome stability, but how H1 functions in these processes is elusive. Here, we report that acetylation of lysine 85 (K85) within the H1 globular domain is a critical post-translational modification that regulates chromatin organization. H1K85 is dynamically acetylated by the acetyltransferase PCAF in response to DNA damage, and this effect is counterbalanced by the histone deacetylase HDAC1. Notably, an acetylation-mimic mutation of H1K85 (H1K85Q) alters H1 binding to the nucleosome and leads to condensed chromatin as a result of increased H1 binding to core histones. In addition, H1K85 acetylation promotes heterochromatin protein 1 (HP1) recruitment to facilitate chromatin compaction. Consequently, H1K85 mutation leads to genomic instability and decreased cell survival upon DNA damage. Together, our data suggest a novel model whereby H1K85 acetylation regulates chromatin structure and preserves chromosome integrity upon DNA damage.

show abstract

Section: Discussionsupporting

confidence: 80%

Histone H1 acetylation at lysine 85 regulates chromatin condensation and genome stability upon DNA damage

Dong

et al. 2018

Nucleic Acids Research

View full text Add to dashboard Cite

show abstract

“…To assess the role of the different Lys residues of ubiquitin in the formation of DDR foci, we set up experimental conditions to markedly reduce ubiquitin expression levels in U2OS cells while retaining cell viability. By using a combination of two different siRNAs, targeting the ubiquitin precursors UBA52 and RPS27A (Adam et al, 2013), we achieved a significant reduction in the formation of ubiquitin conjugates (Figures S4A and S4B) and tested how the ubiquitin knockdown impacts the formation of DDR foci.…”

Section: Chromatin Ubiquitination Induced By Dsbs Is Dependent On Ubk27mentioning

confidence: 98%

RNF168 Promotes Noncanonical K27 Ubiquitination to Signal DNA Damage

Gatti¹,

Pinato²,

Maiolica³

et al. 2015

Cell Reports

164

132

View full text Add to dashboard Cite

Ubiquitination regulates numerous cellular processes by generating a versatile communication system based on eight structurally and functionally different chains linked through distinct residues. Except for K48 and K63, the biological relevance of different linkages is largely unclear. Here, we show that RNF168 ubiquitin ligase promotes noncanonical K27-linked ubiquitination both in vivo and in vitro. We demonstrate that residue K27 of ubiquitin (UbK27) is required for RNF168-dependent chromatin ubiquitination, by targeting histones H2A/H2A.X, and that it is the major ubiquitin-based modification marking chromatin upon DNA damage. Indeed, UbK27 is strictly required for the proper activation of the DNA damage response (DDR) and is directly recognized by crucial DDR mediators, namely 53BP1, Rap80, RNF168, and RNF169. Mutation of UbK27 has dramatic consequences on DDR activation, preventing the recruitment of 53BP1 and BRCA1 to DDR foci. Similarly to the DDR, atypical ubiquitin chains could play unanticipated roles in other crucial ubiquitin-mediated biological processes.

show abstract

“…It is possible that the proposed chromatin-remodeling function of CSB, in addition to its role in coordinating TC-NER, may create a permissive chromatin environment to enable better access to repair factors. Recently, evidence has accumulated that indeed chromatin reorganization is strongly associated to TC-NER (33,51–53). Strikingly, in addition to a role of FACT in stimulating transcription restart in conjunction to TC-NER (33), also a role of FACT in facilitating BER was established (32).…”

Section: Discussionmentioning

confidence: 99%

The transcription-coupled DNA repair-initiating protein CSB promotes XRCC1 recruitment to oxidative DNA damage

Menoni

Wienholz

Theil

et al. 2018

Nucleic Acids Research

View full text Add to dashboard Cite

Transcription-coupled nucleotide excision repair factor Cockayne syndrome protein B (CSB) was suggested to function in the repair of oxidative DNA damage. However thus far, no clear role for CSB in base excision repair (BER), the dedicated pathway to remove abundant oxidative DNA damage, could be established. Using live cell imaging with a laser-assisted procedure to locally induce 8-oxo-7,8-dihydroguanine (8-oxoG) lesions, we previously showed that CSB is recruited to these lesions in a transcription-dependent but NER-independent fashion. Here we showed that recruitment of the preferred 8-oxoG-glycosylase 1 (OGG1) is independent of CSB or active transcription. In contrast, recruitment of the BER-scaffolding protein, X-ray repair cross-complementing protein 1 (XRCC1), to 8-oxoG lesions is stimulated by CSB and transcription. Remarkably, recruitment of XRCC1 to BER-unrelated single strand breaks (SSBs) does not require CSB or transcription. Together, our results suggest a specific transcription-dependent role for CSB in recruiting XRCC1 to BER-generated SSBs, whereas XRCC1 recruitment to SSBs generated independently of BER relies predominantly on PARP activation. Based on our results, we propose a model in which CSB plays a role in facilitating BER progression at transcribed genes, probably to allow XRCC1 recruitment to BER-intermediates masked by RNA polymerase II complexes stalled at these intermediates.

show abstract

Transcription Recovery after DNA Damage Requires Chromatin Priming by the H3.3 Histone Chaperone HIRA

Cited by 254 publications

References 71 publications

Histone H1 acetylation at lysine 85 regulates chromatin condensation and genome stability upon DNA damage

Histone H1 acetylation at lysine 85 regulates chromatin condensation and genome stability upon DNA damage

RNF168 Promotes Noncanonical K27 Ubiquitination to Signal DNA Damage

The transcription-coupled DNA repair-initiating protein CSB promotes XRCC1 recruitment to oxidative DNA damage

Contact Info

Product

Resources

About