Cellular senescence is a mechanism that virtually irreversibly suppresses the proliferative capacity of cells in response to various stress signals. This includes the expression of activated oncogenes, which causes Oncogene-Induced Senescence (OIS). A body of evidence points to the involvement in OIS of chromatin reorganization, including the formation of senescence-associated heterochromatic foci (SAHF). The nuclear lamina (NL) is an important contributor to genome organization and has been implicated in cellular senescence and organismal aging. It interacts with multiple regions of the genome called lamina-associated domains (LADs). Some LADs are cell-type specific, whereas others are conserved between cell types and are referred to as constitutive LADs (cLADs). Here, we used DamID to investigate the changes in genome–NL interactions in a model of OIS triggered by the expression of the common BRAF^V600E oncogene. We found that OIS cells lose most of their cLADS, suggesting the loss of a specific mechanism that targets cLADs to the NL. In addition, multiple genes relocated to the NL. Unexpectedly, they were not repressed, implying the abrogation of the repressive activity of the NL during OIS. Finally, OIS cells displayed an increased association of telomeres with the NL. Our study reveals that senescent cells acquire a new type of LAD organization and suggests the existence of as yet unknown mechanisms that tether cLADs to the NL and repress gene expression at the NL.

细胞衰老是实际上响应各种应激信号不可逆地抑制细胞增殖能力的机制。这包括激活的癌基因的表达，这会导致癌基因诱导的衰老（OIS）。大量证据表明，染色质重组与OIS有关，包括衰老相关的异色病灶（SAHF）的形成。核层（NL）是基因组组织的重要贡献者，并已参与细胞衰老和机体衰老。它与基因组的多个区域相互作用，称为“椎板相关结构域”。一些LAD是特定于细胞类型的，而其他LAD在细胞类型之间是保守的，被称为组成型LAD（cLAD）。这里，^V600E癌基因。我们发现OIS细胞失去了大部分的cLADS，这说明了将cLAD靶向NL的特定机制的丧失。另外，多个基因重定位到NL。出乎意料的是，它们没有被抑制，这意味着在OIS期间NL的抑制活性被取消。最后，OIS细胞显示端粒与NL的关联增加。我们的研究揭示了衰老细胞获得了新型的LAD组织，并暗示了尚不存在的机制将cLAD束缚于NL并抑制NL的基因表达。