A meiosis-specific AAA+ assembly reveals repurposing of ORC during budding yeast gametogenesis
Autor: | Vivek B. Raina, Elisabeth Weir, da Silva Rc, Dongqing Pan, María Ascensión Villar-Fernández, Sarembe A, Gerben Vader, Weir |
---|---|
Rok vydání: | 2019 |
Předmět: |
0303 health sciences
Chemistry Protein subunit DNA replication macromolecular substances Origin of replication Phenotype Cell biology 03 medical and health sciences 0302 clinical medicine Minichromosome maintenance ORC1 Homologous recombination 030217 neurology & neurosurgery Function (biology) 030304 developmental biology |
Popis: | ORC (Orc1-6) is an AAA+ complex that loads the AAA+ MCM helicase to replication origins. Orc1, a subunit of ORC, functionally interacts with budding yeast Pch2, a meiosis-specific AAA+ protein. Pch2 regulates several chromosomal events of gametogenesis, but mechanisms that dictate Pch2 function remain poorly understood. We demonstrate that ORC directly interacts with an AAA+ Pch2 hexamer. The ORC-Pch2 assembly is established without Cdc6, a factor crucial for ORC-MCM binding. Biochemical analysis suggests that Pch2 utilizes ORC’s Cdc6-binding interface and employs its non-enzymatic NH2-terminal domain and AAA+ core to engage ORC. In contrast to phenotypes observed upon Orc1 impairment, nuclear depletion of other subunits of ORC does not lead to Pch2-like phenotypes, indicating that ORC integrity per se is not required to support Pch2 function. We thus reveal functional interplay between Pch2 and ORC, and uncover the repurposing of ORC to establish a non-canonical and meiosis-specific AAA+ assembly. |
Databáze: | OpenAIRE |
Externí odkaz: |