name: Система защиты BREX из Escherichia coli HS и ее вирусные ингибиторы
keyword_list: бактериофаги BREX системы бактериального иммунитета анти-рестрикция Ocr ДНК-мимикрия Т7 Т3 рестрикция-модификация
abstract: BREX is a superfamily of recently described phage defence systems that can be found in more than 10% of bacterial and archaeal genomes. Similar to classical Restriction-Modification systems BREX encodes methyltransferase and methylates the cell’s own genome to discriminate it from incoming viral or plasmid DNA. However, BREX lacks an obvious restriction module and the set of biochemical activities predicted for BREX proteins (ATPase, alkaline phosphatase, Lon-like protease) is not characteristic for any defence system known. This work describes the Type I BREX defence system from E. coli HS, aiming to decipher how it interferes with viral propagation. It is shown that BREX does not prevent adsorption and injection stages, however, inhibits viral DNA accumulation inside infected cells. BREX system proteins interact with each other and form complexes (BrxBCXZ) that to a certain extent resemble complexes of heterooligomeric Type I/III R-M systems. Similar to these systems, the relative orientation of BREX sites in the viral DNA might be important for the efficiency of defence. 
  It was studied how certain phages overcome BREX protection, which led to the discovery of the first anti-BREX proteins. Phage T7 DNA-mimic Ocr – a well-known inhibitor of Type I R-M systems – was shown to be competent in shutting off BREX defence and affecting BREX methylation. BrxX methyltransferase appeared to be a target of Ocr anti-BREX activity. Another anti-BREX discovered in this work – phage T3 SAM Lyase, also known to be active against Type I R-M systems. This enzyme cleaves SAM – an important co-factor of R-M I restriction complexes. Results of this work suggest that SAM is required for BREX activity not only as a donor of methyl groups for methylation but also as a co-factor at the defence stage. An additional mechanism was discovered for T3 SAMase that likely contributes to its anti-restriction activity – SAMase is able to bind SAM synthase (MetK) and thus, in addition to direct enzymatic cleavage, depletes SAM pool through inhibition of its synthesis. Cloning and screening of the large collection of anti-restriction proteins allowed to identify phage P1 DarA as another anti-BREX, as well as to demonstrate that certain anti-restriction proteins can simultaneously downregulate Type IE CRISPR-Cas activity.
chairman_dissertation_council.name: Фазоил
chairman_dissertation_council.surname: Атауллаханов
chairman_dissertation_council.patronymic: Иноятович
chairman_dissertation_council.position: научный руководитель
chairman_dissertation_council.degree: Доктор биологических наук
chairman_dissertation_council.rank: Профессор
chairman_dissertation_council.wos_research_id: J-8076-2012
chairman_dissertation_council.scopus_author_id: 35567335100
chairman_dissertation_council.territory: РОССИЯ
organization_supervisor.name: Виталий
organization_supervisor.surname: Баган
organization_supervisor.patronymic: Анатольевич
organization_supervisor.position: Проректор по научной работе
organization_supervisor.territory: РОССИЯ
rubrics.code: 34.27.21
rubrics.name: Генетика и селекция микроорганизмов
rubrics.code: 34.15.31
rubrics.name: Молекулярная биология вирусов
oecds.code: 01.06.ZE
oecds.name: VIROLOGY
oecds.code: 01.06.CQ
oecds.name: BIOCHEMISTRY & MOLECULAR BIOLOGY
speciality_codes.name: Молекулярная биология
speciality_codes.code: 03.01.03
supervisors.fio: Северинов К.В
supervisors.scientific_degree: Доктор биологических наук
supervisors.speciality_code: Молекулярная биология
supervisors.responsible_type: Научный руководитель
protection_organization.short_name: МФТИ, ФИЗТЕХ
protection_organization.name: ФЕДЕРАЛЬНОЕ ГОСУДАРСТВЕННОЕ АВТОНОМНОЕ ОБРАЗОВАТЕЛЬНОЕ УЧРЕЖДЕНИЕ ВЫСШЕГО ОБРАЗОВАНИЯ "МОСКОВСКИЙ ФИЗИКО-ТЕХНИЧЕСКИЙ ИНСТИТУТ (НАЦИОНАЛЬНЫЙ ИССЛЕДОВАТЕЛЬСКИЙ УНИВЕРСИТЕТ)"
protection_organization.ogrn: 1027739386135
protection_organization.supervisor_name: ДМИТРИЙ
protection_organization.supervisor_surname: ЛИВАНОВ
protection_organization.supervisor_patronymic: ВИКТОРОВИЧ
protection_organization.organization_type: Организация
protection_organization.okogu: Министерство науки и высшего образования Российской Федерации
protection_organization.okopf: Федеральные государственные автономные учреждения
author_organization.short_name: СКОЛКОВСКИЙ ИНСТИТУТ НАУКИ И ТЕХНОЛОГИЙ
author_organization.name: АВТОНОМНАЯ НЕКОММЕРЧЕСКАЯ ОБРАЗОВАТЕЛЬНАЯ ОРГАНИЗАЦИЯ ВЫСШЕГО ОБРАЗОВАНИЯ "СКОЛКОВСКИЙ ИНСТИТУТ НАУКИ И ТЕХНОЛОГИЙ"
author_organization.ogrn: 1115000005922
author_organization.supervisor_name: АЛЕКСАНДР
author_organization.supervisor_surname: КУЛЕШОВ
author_organization.supervisor_patronymic: ПЕТРОВИЧ
author_organization.organization_type: Организация
author_organization.okogu: Организации, учрежденные юридическими лицами или гражданами, или юридическими лицами и гражданами совместно
author_organization.okopf: Автономные некоммерческие организации