Karamysheva Zemfira, Díaz-Martínez Laura A, Warrington Ross, Yu Hongtao
a Department of Physiology; University of Texas Southwestern Medical Center ; Dallas , TX , USA.
Cell Cycle. 2015;14(12):1873-83. doi: 10.1080/15384101.2015.1039209.
Genome stability is ensured by multiple surveillance mechanisms that monitor the duplication, segregation, and integrity of the genome throughout the cell cycle. Depletion of components of the spliceosome, a macromolecular machine essential for mRNA maturation and gene expression, has been associated with increased DNA damage and cell cycle defects. However, the specific role for the spliceosome in these processes has remained elusive, as different cell cycle defects have been reported depending on the specific spliceosome subunit depleted. Through a detailed cell cycle analysis after spliceosome depletion, we demonstrate that the spliceosome is required for progression through multiple phases of the cell cycle. Strikingly, the specific cell cycle phenotype observed after spliceosome depletion correlates with the extent of depletion. Partial depletion of a core spliceosome component results in defects at later stages of the cell cycle (G2 and mitosis), whereas a more complete depletion of the same component elicits an early cell cycle arrest in G1. We propose a quantitative model in which different functional dosages of the spliceosome are required for different cell cycle transitions.
基因组稳定性由多种监测机制确保，这些机制在整个细胞周期中监测基因组的复制、分离和完整性。剪接体是mRNA成熟和基因表达所必需的大分子机器，其成分的缺失与DNA损伤增加和细胞周期缺陷有关。然而，剪接体在这些过程中的具体作用仍然难以捉摸，因为根据所缺失的特定剪接体亚基，已报道了不同的细胞周期缺陷。通过对剪接体缺失后的细胞周期进行详细分析，我们证明剪接体是细胞周期多个阶段进展所必需的。引人注目的是，剪接体缺失后观察到的特定细胞周期表型与缺失程度相关。核心剪接体成分的部分缺失导致细胞周期后期（G2期和有丝分裂期）出现缺陷，而同一成分更完全的缺失则引发G1期早期细胞周期停滞。我们提出了一个定量模型，其中不同的细胞周期转换需要不同功能剂量的剪接体。
