The Department of Cell and Molecular Biology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America.
PLoS One. 2013 Jul 24;8(7):e69169. doi: 10.1371/journal.pone.0069169. Print 2013.
The nuclear lamins play important roles in the structural organization and function of the metazoan cell nucleus. Recent studies on B-type lamins identified a requirement for lamin B1 (LB1) in the regulation of cell proliferation in normal diploid cells. In order to further investigate the function of LB1 in proliferation, we disrupted its normal expression in U-2 OS human osteosarcoma and other tumor cell lines. Silencing LB1 expression induced G1 cell cycle arrest without significant apoptosis. The arrested cells are unable to mount a timely and effective response to DNA damage induced by UV irradiation. Several proteins involved in the detection and repair of UV damage by the nucleotide excision repair (NER) pathway are down-regulated in LB1 silenced cells including DDB1, CSB and PCNA. We propose that LB1 regulates the DNA damage response to UV irradiation by modulating the expression of specific genes and activating persistent DNA damage signaling. Our findings are relevant to understanding the relationship between the loss of LB1 expression, DNA damage signaling, and replicative senescence.
核纤层蛋白在真核细胞核的结构组织和功能中发挥着重要作用。最近对 B 型核纤层蛋白的研究表明，核纤层蛋白 B1（LB1）在正常二倍体细胞的细胞增殖调控中起作用。为了进一步研究 LB1 在增殖中的功能，我们在 U-2 OS 人骨肉瘤和其他肿瘤细胞系中破坏了其正常表达。沉默 LB1 表达诱导 G1 期细胞周期停滞，而没有明显的细胞凋亡。被阻滞的细胞无法对 UV 照射诱导的 DNA 损伤及时做出有效的反应。在 LB1 沉默的细胞中，包括 DDB1、CSB 和 PCNA 在内的几种参与核苷酸切除修复（NER）途径检测和修复 UV 损伤的蛋白下调。我们提出 LB1 通过调节特定基因的表达和激活持续的 DNA 损伤信号来调节对 UV 照射的 DNA 损伤反应。我们的发现与理解 LB1 表达丧失、DNA 损伤信号和复制性衰老之间的关系有关。
