ASH1L-MRG15 methyltransferase deposits H3K4me3 and FACT for damage verification in nucleotide excision repair

To recognize DNA adducts, nucleotide excision repair (NER) deploys the XPC sensor, which detects damage-induced helical distortions, followed by engagement of TFIIH for lesion verification. Accessory players ensure that this factor handover takes place in chromatin where DNA is tightly wrapped around histones. Here, we describe how the histone methyltransferase ASH1L, once activated by MRG15, helps XPC and TFIIH to navigate through chromatin and induce global-genome NER hotspots. Upon UV irradiation, ASH1L adds H3K4me3 all over the genome (except in active gene promoters), thus priming chromatin for XPC relocations from native to damaged DNA. The ASH1L-MRG15 complex further recruits the histone chaperone FACT to DNA lesions. In the absence of ASH1L, MRG15 or FACT, XPC is misplaced and persists on damaged DNA without being able to deliver the lesions to TFIIH. We conclude that ASH1L-MRG15 makes damage verifiable by the NER machinery through the sequential deposition of H3K4me3 and FACT

To incise or not and where: SET-domain methyltransferases know

The concept of the histone code posits that histone modifications regulate gene functions once interpreted by epigenetic readers. A well-studied case is trimethylation of lysine 4 of histone H3 (H3K4me3), which is enriched at gene promoters. However, H3K4me3 marks are not needed for the expression of most genes, suggesting extra roles, such as influencing the 3D genome architecture. Here, we highlight an intriguing analogy between the H3K4me3-dependent induction of double-strand breaks in several recombination events and the impact of this same mark on DNA incisions for the repair of bulky lesions. We propose that Su(var)3–9, Enhancer-of-zeste and Trithorax (SET)-domain methyltransferases generate H3K4me3 to guide nucleases into chromatin spaces, the favorable accessibility of which ensures that DNA break intermediates are readily processed, thereby safeguarding genome stability

Animal dietary exposure in the risk assessment of feed derived from genetically modified plants

EFSA carries out the risk assessment of genetically modified plants for food and feed uses under Regulation (EU) No 503/2013. Exposure assessment – anticipated intake/extend of use shall be an essential element of the risk assessment of genetically modified feeds, as required by Regulation (EU) No 503/2013. Estimates of animal dietary exposure to newly expressed proteins should be determined to cover average consumption across all the different species, age, physiological and productive phases of farmed and companion animals, and identify and consider particular consumer groups with expected higher exposure. This statement is aimed at facilitating the reporting of the information that applicants need to provide on expected animal dietary exposure to newly expressed proteins and to increase harmonisation of the application dossiers to be assessed by the EFSA GMO Panel. Advice is provided on the selection of proper feed consumption and feed concentration data, and on the reporting of exposure’s estimates. An overview of the different uncertainties that may be linked to the estimations is provided. This statement also explains how to access an Excel calculator which should be used in future applications as basis to provide a more consistent presentation of estimates of expected animal dietary exposure

Assessment of genetically modified oilseed rape GT73 for renewal authorisation under Regulation (EC) No 1829/2003 (application EFSA‐GMO‐RX‐002)

Following the submission of application EFSA-GMO-RX-002 under Regulation (EC) No 1829/2003 from Monsanto Company, the Panel on Genetically Modified Organisms of EFSA (GMO) was asked to deliver a scientific risk assessment on the data submitted in the context of the renewal of authorisation application for the herbicide-tolerant genetically modified oilseed rape GT73. The data received in the context of this renewal application contained post-market environmental monitoring reports, a systematic search and evaluation of literature, updated bioinformatic analyses and additional documents or studies performed by or on behalf of the applicant. The GMO Panel assessed these data for possible new hazards, modified exposure or new scientific uncertainties identified during the authorisation period and not previously assessed in the context of the original application. Under the assumption that the DNA sequence of the event in oilseed rape GT73 considered for renewal of authorisation is identical to the sequence of the originally assessed event, the GMO Panel concludes that there is no evidence in renewal application EFSA-GMO-RX-002 for new hazards, modified exposure or scientific uncertainties that would change the conclusions of the original risk assessment on oilseed rape GT73

Applicability of the EFSA Opinion on site-directed nucleases type 3 for the safety assessment of plants developed using site-directed nucleases type 1 and 2 and oligonucleotide directed mutagenesis

© 2020 European Food Safety Authority.The European Commission requested the EFSA Panel on Genetically Modified Organisms (GMO) to assess whether section 4 (hazard identification) and the conclusions of EFSA's Scientific opinion on the risk assessment of plants developed using zinc finger nuclease type 3 technique (ZFN‐3) and other site‐directed nucleases (SDN) with similar function are valid for plants developed via SDN‐1, SDN‐2 and oligonucleotide‐directed mutagenesis (ODM). In delivering this Opinion, the GMO Panel compared the hazards associated with plants produced via SDN‐1, SDN‐2 and ODM with those associated with plants obtained via both SDN‐3 and conventional breeding. Unlike for SDN‐3 methods, the application of SDN‐1, SDN‐2 and ODM approaches aims to modify genomic sequences in a way which can result in plants not containing any transgene, intragene or cisgene. Consequently, the GMO Panel concludes that those considerations which are specifically related to the presence of a transgene, intragene or cisgene included in section 4 and the conclusions of the Opinion on SDN‐3 are not relevant to plants obtained via SDN‐1, SDN‐2 or ODM as defined in this Opinion. Overall, the GMO Panel did not identify new hazards specifically linked to the genomic modification produced via SDN‐1, SDN‐2 or ODM as compared with both SDN‐3 and conventional breeding. Furthermore, the GMO Panel considers that the existing Guidance for risk assessment of food and feed from genetically modified plants and the Guidance on the environmental risk assessment of genetically modified plants are sufficient but are only partially applicable to plants generated via SDN‐1, SDN‐2 or ODM. Indeed, those guidance documents’ requirements that are linked to the presence of exogenous DNA are not relevant for the risk assessment of plants developed via SDN‐1, SDN‐2 or ODM approaches if the genome of the final product does not contain exogenous DNA

Statement on in vitro protein digestibility tests in allergenicity and protein safety assessment of genetically modified plants

This statement supplements and updates the GMO Panel guidance document on allergenicity of genetically modified (GM) plants published in 2017. In that guidance document, the GMO Panel considered that additional investigations on in vitro protein digestibility were needed before providing any additional recommendations in the form of guidance to applicants. Thus, an interim phase was proposed to assess the utility of an enhanced in vitro digestion test, as compared to the classical pepsin resistance test. Historically, resistance to degradation by pepsin using the classical pepsin resistance test has been considered as additional information, in a weight-of-evidence approach, for the assessment of allergenicity and toxicity of newly expressed proteins in GM plants. However, more recent evidence does not support this test as a good predictor of allergenic potential for hazard. Furthermore, there is a need for more reliable systems to predict the fate of the proteins in the gastrointestinal tract and how they interact with the relevant human cells. Nevertheless, the classical pepsin resistance test can still provide some information on the physicochemical properties of novel proteins relating to their stability under acidic conditions. But other methods can be used to obtain data on protein's structural and/or functional integrity. It is acknowledged that the classical pepsin resistance test is embedded into international guidelines, e.g. Codex Alimentarius and Regulation (EU) No 503/2013. For future development, a deeper understanding of protein digestion in the gastrointestinal tract could enable the framing of more robust strategies for the safety assessment of proteins. Given the high complexity of the digestion and absorption process of dietary proteins, it is needed to clarify and identify the aspects that could be relevant to assess potential risks of allergenicity and toxicity of proteins. To this end, a series of research questions to be addressed are also formulated in this statement

Assessment of genetically modified soybean MON 87701 × MON 89788 for renewal authorisation under Regulation (EC) No 1829/2003 (application EFSA‐GMO‐RX‐022)

Following the submission of application EFSA-GMO-RX-022 under Regulation (EC) No 1829/2003 from Bayer CropScience LP, the Panel on Genetically Modified Organisms of the European Food Safety Authority was asked to deliver a scientific risk assessment on the data submitted in the context of the renewal of authorisation application for the insect-resistant and herbicide-tolerant genetically modified soybean MON 87701 × MON 89788, for food and feed uses, excluding cultivation within the European Union. The data received in the context of this renewal application contained post-market environmental monitoring reports, a systematic search and evaluation of literature, updated bioinformatic analyses, and additional documents or studies performed by or on behalf of the applicant. The GMO Panel assessed these data for possible new hazards, modified exposure or new scientific uncertainties identified during the authorisation period and not previously assessed in the context of the original application. Under the assumption that the DNA sequences of the events in soybean MON 87701 × MON 89788 considered for renewal are identical to the sequences of the originally assessed event, the GMO Panel concludes that there is no evidence in renewal application EFSA-GMO-RX-022 for new hazards, modified exposure or scientific uncertainties that would change the conclusions of the original risk assessment on soybean MON 87701 × MON 89788

Assessment of genetically modified soybean MON 87701 for renewal authorisation under Regulation (EC) No 1829/2003 (application EFSA‐GMO‐RX‐021)

Following the submission of application EFSA-GMO-RX-021 under Regulation (EC) No 1829/2003 from Bayer CropScience LP, the Panel on Genetically Modified Organisms of the European Food Safety Authority was asked to deliver a scientific risk assessment on the data submitted in the context of the renewal of authorisation application for the insect-resistant genetically modified soybean MON 87701, for food and feed uses, excluding cultivation within the European Union. The data received in the context of this renewal application contained post-market environmental monitoring reports, a systematic search and evaluation of literature, updated bioinformatic analyses and additional documents or studies performed by or on behalf of the applicant. The GMO Panel assessed these data for possible new hazards, modified exposure or new scientific uncertainties identified during the authorisation period and not previously assessed in the context of the original application. Under the assumption that the DNA sequences of the event in soybean MON 87701 considered for renewal is identical to the sequences of the originally assessed event, the GMO Panel concludes that there is no evidence in renewal application EFSA-GMO-RX-021 for new hazards, modified exposure or scientific uncertainties that would change the conclusions of the original risk assessment on soybean MON 87701

Assessment of genetically modified soybean 40‐3‐2 for renewal authorisation under Regulation (EC) No 1829/2003 (application EFSA‐GMO‐RX‐023)

Following the submission of application EFSA-GMO-RX-023 under Regulation (EC) No 1829/2003 from Bayer Agriculture BV on behalf of Bayer CropScience LP, the Panel on Genetically Modified Organisms of the European Food Safety Authority was asked to deliver a scientific risk assessment on the data submitted in the context of the renewal of authorisation application for the herbicide-tolerant genetically modified soybean 40-3-2, for food and feed uses, excluding cultivation within the European Union. The data received in the context of this renewal application contained post-market environmental monitoring reports, a systematic search and evaluation of literature, updated bioinformatic analyses, and additional documents or studies performed by or on behalf of the applicant. The GMO Panel assessed these data for possible new hazards, modified exposure or new scientific uncertainties identified during the authorisation period and not previously assessed in the context of the original application. Under the assumption that the DNA sequence of the event in soybean 40-3-2 considered for renewal is identical to the sequence of the originally assessed event, the GMO Panel concludes that there is no evidence in renewal application EFSA-GMO-RX-023 for new hazards, modified exposure or scientific uncertainties that would change the conclusions of the original risk assessment on soybean 40-3-2

Assessment of genetically modified cotton 281‐24‐236 × 3006‐210‐23 for renewal authorisation under Regulation (EC) No 1829/2003 (application EFSA‐GMO‐RX‐019)

Following the submission of application EFSA-GMO-RX-019 under Regulation (EC) No 1829/2003 from Corteva Agriscience LLC represented by Corteva Agriscience Belgium B.V., the Panel on Genetically Modified Organisms of the European Food Safety Authority was asked to deliver a scientific risk assessment on the data submitted in the context of the renewal of authorisation application for the insect resistant genetically modified cotton 281-24-236 × 3006-210-23, for food and feed uses, excluding cultivation within the European Union. The data received in the context of this renewal application contained post-market environmental monitoring reports, a systematic search and evaluation of literature, updated bioinformatic analyses, and additional documents or studies performed by or on behalf of the applicant. The GMO Panel assessed these data for possible new hazards, modified exposure or new scientific uncertainties identified during the authorisation period and not previously assessed in the context of the original application. The GMO Panel concludes that there is no evidence in renewal application EFSA-GMO-RX-019 for new hazards, modified exposure or scientific uncertainties that would change the conclusions of the original risk assessment on cotton 281-24-236 × 3006-210-23