Remeseiro Silvia, Cuadrado Ana, Kawauchi Shimako, Calof Anne L, Lander Arthur D, Losada Ana
Chromosome Dynamics Group, Molecular Oncology Programme, Spanish National Cancer Research Centre (CNIO), Melchor Fernández Almagro 3, 28029 Madrid, Spain.
Biochim Biophys Acta. 2013 Dec;1832(12):2097-102. doi: 10.1016/j.bbadis.2013.07.020. Epub 2013 Aug 3.
Cornelia de Lange Syndrome (CdLS) is a genetic disorder linked to mutations in cohesin and its regulators. To date, it is unclear which function of cohesin is more relevant to the pathology of the syndrome. A mouse heterozygous for the gene encoding the cohesin loader Nipbl recapitulates many features of CdLS. We have carefully examined Nipbl deficient cells and here report that they have robust cohesion all along the chromosome. DNA replication, DNA repair and chromosome segregation are carried out efficiently in these cells. While bulk cohesin loading is unperturbed, binding to certain promoters such as the Protocadherin genes in brain is notably affected and alters gene expression. These results provide further support for the idea that developmental defects in CdLS are caused by deregulated transcription and not by malfunction of cohesion-related processes.
科妮莉亚·德朗格综合征（CdLS）是一种与黏连蛋白及其调节因子突变相关的遗传性疾病。迄今为止，尚不清楚黏连蛋白的哪种功能与该综合征的病理更为相关。编码黏连蛋白装载蛋白Nipbl的基因杂合的小鼠概括了CdLS的许多特征。我们仔细检查了Nipbl缺陷细胞，在此报告它们在整个染色体上都具有强大的黏连作用。这些细胞中的DNA复制、DNA修复和染色体分离均有效进行。虽然大量黏连蛋白的装载未受干扰，但与某些启动子（如大脑中的原钙黏蛋白基因）的结合受到显著影响，并改变了基因表达。这些结果为CdLS的发育缺陷是由转录失调而非黏连相关过程的功能障碍引起这一观点提供了进一步支持。
