Schmidt Kristina H, Kolodner Richard D
Ludwig Institute for Cancer Research, University of California-San Diego School of Medicine, La Jolla, California 92093, USA.
Mol Cell Biol. 2004 Apr;24(8):3213-26. doi: 10.1128/MCB.24.8.3213-3226.2004.
The Rrm3 DNA helicase of Saccharomyces cerevisiae interacts with proliferating cell nuclear antigen and is required for replication fork progression through ribosomal DNA repeats and subtelomeric and telomeric DNA. Here, we show that rrm3 srs2 and rrm3 sgs1 mutants, in which two different DNA helicases have been inactivated, exhibit a severe growth defect and undergo frequent cell death. Cells lacking Rrm3 and Srs2 arrest in the G(2)/M phase of the cell cycle with 2N DNA content and frequently contain only a single nucleus. The phenotypes of rrm3 srs2 and rrm3 sgs1 mutants were suppressed by disrupting early steps of homologous recombination. These observations identify Rrm3 as a new member of a network of pathways, involving Sgs1 and Srs2 helicases and Mus81 endonuclease, suggested to act during repair of stalled replication forks.
酿酒酵母的Rrm3 DNA解旋酶与增殖细胞核抗原相互作用,是复制叉通过核糖体DNA重复序列以及亚端粒和端粒DNA进行延伸所必需的。在此,我们表明,rrm3 srs2和rrm3 sgs1突变体(其中两种不同的DNA解旋酶已失活)表现出严重的生长缺陷并频繁发生细胞死亡。缺乏Rrm3和Srs2的细胞在细胞周期的G(2)/M期停滞,DNA含量为2N,且通常仅含有一个细胞核。通过破坏同源重组的早期步骤,rrm3 srs2和rrm3 sgs1突变体的表型得到了抑制。这些观察结果确定Rrm3是一个途径网络的新成员,该网络涉及Sgs1和Srs2解旋酶以及Mus81核酸内切酶,推测它们在停滞复制叉的修复过程中发挥作用。