{"id":"96a56330-a974-5822-aa2a-84a9116b2bba","stable_key":"e37461ea-ea5d-5e2c-8091-138305f6dd70:l-aspartate-sdh-pyrimidine-stress","predicate":"constrains","statement":"SDH loss increased succinate, impaired aspartate entry into pyrimidine synthesis and produced nucleotide insufficiency with replication stress and increased ATR-inhibitor sensitivity.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"9eaf6a4d-d070-584e-a533-95dda97a2e3a","mechanism_event_label":"The effect propagated from metabolism into DNA replication control.","subject":{"id":"6ba5dcfe-4482-5f80-962a-19d8d5d097f2","slug":"human-sdh-impairment","display_name":"SDH inhibition or loss in human cell models","entity_type_key":"cellular_process"},"object":{"id":"ca5270e5-722b-5dec-bf87-ba2442660b54","slug":"human-sdh-deficient-pyrimidines","display_name":"Pyrimidine production after human-cell SDH impairment","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"9eaf6a4d-d070-584e-a533-95dda97a2e3a","stable_key":"e37461ea-ea5d-5e2c-8091-138305f6dd70:l-aspartate-sdh-pyrimidine-stress-event","event_type":"observed_relationship","label":"The effect propagated from metabolism into DNA replication control.","description":"SDH loss increased succinate, impaired aspartate entry into pyrimidine synthesis and produced nucleotide insufficiency with replication stress and increased ATR-inhibitor sensitivity.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"6ba5dcfe-4482-5f80-962a-19d8d5d097f2","slug":"human-sdh-impairment","display_name":"SDH inhibition or loss in human cell models","entity_type_key":"cellular_process"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"ca5270e5-722b-5dec-bf87-ba2442660b54","slug":"human-sdh-deficient-pyrimidines","display_name":"Pyrimidine production after human-cell SDH impairment","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"0a0923d3-72b7-5d6a-bf3a-5a7a3071a09b","slug":"l-aspartate","display_name":"L-Aspartate","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"462f63ce-a2c1-5312-9c14-70b8b12e1d6e","slug":"succinate","display_name":"Succinate","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"64cc3b93-3e99-5221-bd91-049d190e54c7","slug":"cad","display_name":"Human CAD multifunctional pyrimidine synthesis enzyme","entity_type_key":"protein"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"bf3d947d-8d8b-5383-8b88-f5f4d649809f","slug":"sdhb","display_name":"Human succinate dehydrogenase iron-sulfur subunit / SDHB","entity_type_key":"protein"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":5,"notes":""},{"entity":{"id":"fe8d147a-fd3c-5768-ae24-f6c4fbd2ae8d","slug":"atr","display_name":"Human ATR kinase","entity_type_key":"protein"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":6,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; 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