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.

细胞衰老是一种几乎不可逆地抑制细胞响应各种压力信号的增殖能力的机制。这包括激活致癌基因的表达，这会导致致癌基因诱导的衰老 (OIS)。大量证据表明染色质重组参与了 OIS，包括衰老相关异染色质灶 (SAHF) 的形成。核层 (NL) 是基因组组织的重要贡献者，并与细胞衰老和机体衰老有关。它与称为层板相关域 (LAD) 的基因组的多个区域相互作用。一些 LADs 是细胞类型特异性的，而另一些在细胞类型之间是保守的，被称为组成型 LADs (cLADs)。这里，^V600E癌基因。我们发现 OIS 细胞失去了大部分 cLADS，这表明将 cLAD 靶向 NL 的特定机制丢失了。此外，多个基因重新定位到 NL。出乎意料的是，他们没有被镇压，这意味着在 OIS 期间废除了 NL 的镇压活动。最后，OIS 细胞显示端粒与 NL 的关联增加。我们的研究表明，衰老细胞获得了一种新型的 LAD 组织，并表明存在将 cLAD 束缚在 NL 并抑制 NL 的基因表达的未知机制。