Hu F, Alcasabas A A, Elledge S J
Verna and Mars McLean Department of Biochemistry and Molecular Biology, Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas 77030, USA.
Genes Dev. 2001 May 1;15(9):1061-6. doi: 10.1101/gad.873201.
Yeast defective in the checkpoint kinase Rad53 fail to recover from transient DNA replication blocks and synthesize intact chromosomes. The effectors of Rad53 relevant to this recovery process are unknown. Here we report that overproduction of the chromatin assembly factor Asf1 can suppress the Ts phenotype of mrc1rad53 double mutants and the HU sensitivity of rad53 mutants. Eliminating silencing also suppresses this lethality, further implicating chromatin structure in checkpoint function. We find that Asf1 and Rad53 exist in a dynamic complex that dissociates in response to replication blocks and DNA damage. Thus, checkpoint pathways directly regulate chromatin assembly to promote survival in response to DNA damage and replication blocks.
在检查点激酶Rad53中存在缺陷的酵母无法从短暂的DNA复制阻滞中恢复，也无法合成完整的染色体。与这一恢复过程相关的Rad53效应因子尚不清楚。在此我们报告，染色质组装因子Asf1的过量表达可以抑制mrc1rad53双突变体的温度敏感（Ts）表型以及rad53突变体对羟基脲（HU）的敏感性。消除沉默也能抑制这种致死性，这进一步表明染色质结构与检查点功能有关。我们发现Asf1和Rad53存在于一个动态复合物中，该复合物会响应复制阻滞和DNA损伤而解离。因此，检查点通路直接调节染色质组装，以促进细胞在应对DNA损伤和复制阻滞时的存活。
