Nuclear envelope membrane proteins and nuclear structure

描述(申请人提供)：核膜(NE)长期以来一直被认为是真核细胞基因组的守门人，限制了基因组的访问，仅限于那些能够通过核孔复合体(NPC)穿越NE的分子。然而，越来越明显的是，NE在基因组组织中发挥着积极和必要的作用，而不仅仅是提供简单的DMA区隔。NE相关的复合体对于维持染色质结构、基因调控和DMA复制是重要的。NE结构的破坏可能导致这些过程的失调。这项建议侧重于NE膜蛋白在维持NE提供的结构完整性方面的作用，特别是NE膜蛋白的跨膜(TM)和管腔结构域的作用。

DESCRIPTION (provided by applicant): The nuclear envelope (NE) has long been appreciated as a gatekeeper to the genome of eukaryotic cells, restricting genomic access only to those molecules capable of traversing the NE via nuclear pore complexes (NPCs). It is increasingly evident, however, that the NE performs active and essential roles in genomic organization beyond providing simple compartmentalization of DMA. NE-associated complexes are important for maintenance of chromatin structure, gene regulation, and DMA replication. Disruption of the NE structure can lead to disregulation of these processes. This proposal focuses on the role of NE membrane proteins in maintaining the structural integrity provided by the NE, with a particular focus on the role of the transmembrane (TM) and lumenal domains of NE membrane proteins.