Interplay and Quality Control of DNA Damage Repair Mechanisms

Eppink, Berina; Essers, Jeroen; Kanaar, Roland

doi:10.1002/9783527639991.ch16

Cited by 3 publications

(5 citation statements)

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“…Ku70/Ku80 attracts the catalytic sub-unit of DNAdependent protein kinase and activates its kinase activity (summarized by ref. 19). This process initiates a cascade of events, which leads to recovery of damaged DNA.…”

mentioning

confidence: 99%

Coilin is rapidly recruited to UVA-induced DNA lesions and γ-radiation affects localized movement of Cajal bodies

Bártová

Foltánková

Legartová

et al. 2014

Nucleus

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mentioning

confidence: 99%

Coilin is rapidly recruited to UVA-induced DNA lesions and γ-radiation affects localized movement of Cajal bodies

Bártová

Foltánková

Legartová

et al. 2014

Nucleus

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“…Here, we additionally specified HP1β functioning at DNA lesions by its interaction with UBF1 (Figures 1 B, 4 E, and 6 A-C). Moreover, we showed that recruitment and interaction of HP1β with UBF1 at DNA lesions is a specific event appearing simultaneously with CPDs (Figure 2 C), recognized by the nucleotide excision repair pathway [ 31 , 32 ]. This process is not accompanied by UBF1 dimerization at DNA lesions (Figure 4 B).…”

Section: Discussionmentioning

confidence: 99%

“…As UBF1 is a ribosomal gene transcription factor, the theory of transcription-coupled repair (TCR) (summarized by [ 31 , 35 ]) is relevant to our investigations. We showed that UBF1 colocalizes with CPDs, which are recognized by the nucleotide excision repair pathway, and it is well known that TCR is a variant of nucleotide excision repair [ 31 ]. The TCR pathway is associated with protein-coding genes, but we observed pronounced UBF1 recruitment in the nucleolus, where ribosomal genes reside (see detail of UBF1 and nucleoli in Figures 1 A,B and 3 C).…”

Section: Discussionmentioning

confidence: 99%

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HP1β-dependent recruitment of UBF1 to irradiated chromatin occurs simultaneously with CPDs

Stixová

Sehnalová

Legartová

et al. 2014

Epigenetics & Chromatin

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BackgroundThe repair of spontaneous and induced DNA lesions is a multistep process. Depending on the type of injury, damaged DNA is recognized by many proteins specifically involved in distinct DNA repair pathways.ResultsWe analyzed the DNA-damage response after ultraviolet A (UVA) and γ irradiation of mouse embryonic fibroblasts and focused on upstream binding factor 1 (UBF1), a key protein in the regulation of ribosomal gene transcription. We found that UBF1, but not nucleolar proteins RPA194, TCOF, or fibrillarin, was recruited to UVA-irradiated chromatin concurrently with an increase in heterochromatin protein 1β (HP1β) level. Moreover, Förster Resonance Energy Transfer (FRET) confirmed interaction between UBF1 and HP1β that was dependent on a functional chromo shadow domain of HP1β. Thus, overexpression of HP1β with a deleted chromo shadow domain had a dominant-negative effect on UBF1 recruitment to UVA-damaged chromatin. Transcription factor UBF1 also interacted directly with DNA inside the nucleolus but no interaction of UBF1 and DNA was confirmed outside the nucleolus, where UBF1 recruitment to DNA lesions appeared simultaneously with cyclobutane pyrimidine dimers; this occurrence was cell-cycle-independent.ConclusionsWe propose that the simultaneous presence and interaction of UBF1 and HP1β at DNA lesions is activated by the presence of cyclobutane pyrimidine dimers and mediated by the chromo shadow domain of HP1β. This might have functional significance for nucleotide excision repair.Electronic supplementary materialThe online version of this article (doi:10.1186/1756-8935-7-39) contains supplementary material, which is available to authorized users.

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“…Together, these processes are responsible for the repair of single-stranded DNA lesions induced by genotoxic factors. 1 Homologous recombination repair (HRR) and non-homologous end-joining (NHEJ), two fundamental cell cycle-dependent mechanisms, recognize and repair double-strand breaks (DSBs) (summarized by 2,3 ). Standard NHEJ, which can appear at all cell cycle phases, involves the mobilization of the catalytic subunit of DNA-dependent protein kinase (DNA-PK) and the activation of the XRCC4/DNA ligase IV complex.…”

Section: Introductionmentioning

confidence: 99%

Localized movement and morphology of UBF1-positive nucleolar regions are changed by γ-irradiation in G2 phase of the cell cycle

Sorokin

Stixová

Sehnalová

et al. 2015

Nucleus

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(2015) Localized movement and morphology of UBF1-positive nucleolar regions are changed by γ-irradiation in G2 phase of the cell cycle, Nucleus, 6:4, 301-313, DOI: 10.1080/19491034.2015 To link to this article: https://doi.org/10. 1080/19491034.2015 Abbreviations: 53BP1, p53-binding protein; ACT-D, actinomycin D; ATM, ataxia telangiectasia mutated; ATR, ATM and Rad3-related protein; AR, area ratio (area of nucleolus/area of nucleus); BrdU, 5-bromo-2 0 -deoxy-uridine; BER, base excision repair; CBs, Cajal bodies; DDR, DNA damage response; CPDs, cyclobutane pyrimidine dimers; DMEM, Dulbecco's modified Eagle's medium; DNA-PK, DNA-dependent protein kinase; DSBs, double-strand breaks; FA, foci area; NF, number of foci; FI, fluorescence intensity; FRAP, fluorescence recovery after photobleaching; GGR, global genome repair; GFP, green fluorescence protein; HP1, heterochromatin protein 1; HR, homologous recombination; HRR, homologous recombination repair; iMEFs, immortalized mouse embryonic fibroblasts; LR, local radius; NBs, nuclear bodies; NER, nucleotide excision repair; NHEJ, non-homologous end-joining; nA, nucleolus area; NA, nucleus area; PBS, phosphate-buffered saline; P2A, compactness; PCR, polymerase chain reaction; PML, promyelocytic leukemia bodies; rDNA, ribosomal DNA; RNA Pol II, RNA polymerase II; ROI, region of interest; RPA, replicationrelated protein A; SEM, standard error of the mean; SDS, sodium dodecyl sulfate; TCR, transcription-coupled NER; UBF1, upstream binding factor 1; UV, ultraviolet.The nucleolus is a well-organized site of ribosomal gene transcription. Moreover, many DNA repair pathway proteins, including ATM, ATR kinases, MRE11, PARP1 and Ku70/80, localize to the nucleolus (Moore et al., 2011). We analyzed the consequences of DNA damage in nucleoli following ultraviolet A (UVA), C (UVC), or g-irradiation in order to test whether and how radiation-mediated genome injury affects local motion and morphology of nucleoli. Because exposure to radiation sources can induce changes in the pattern of UBF1-positive nucleolar regions, we visualized nucleoli in living cells by GFP-UBF1 expression for subsequent morphological analyses and local motion studies. UVA radiation, but not 5 Gy of g-rays, induced apoptosis as analyzed by an advanced computational method. In non-apoptotic cells, we observed that g-radiation caused nucleolar re-positioning over time and changed several morphological parameters, including the size of the nucleolus and the area of individual UBF1-positive foci. Radiation-induced nucleoli rearrangement was observed particularly in G2 phase of the cell cycle, indicating repair of ribosomal genes in G2 phase and implying that nucleoli are less stable, thus sensitive to radiation, in G2 phase.

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Interplay and Quality Control of DNA Damage Repair Mechanisms

Cited by 3 publications

References 91 publications

Coilin is rapidly recruited to UVA-induced DNA lesions and γ-radiation affects localized movement of Cajal bodies

Coilin is rapidly recruited to UVA-induced DNA lesions and γ-radiation affects localized movement of Cajal bodies

HP1β-dependent recruitment of UBF1 to irradiated chromatin occurs simultaneously with CPDs

Localized movement and morphology of UBF1-positive nucleolar regions are changed by γ-irradiation in G2 phase of the cell cycle

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