DPB11, WHICH INTERACTS WITH DNA-POLYMERASE II(EPSILON) IN SACCHAROMYCES-CEREVISIAE, HAS A DUAL ROLE IN S-PHASE PROGRESSION AND AT A CELL-CYCLE CHECKPOINT
DPB11, WHICH INTERACTS WITH DNA-POLYMERASE II(EPSILON) IN SACCHAROMYCES-CEREVISIAE, HAS A DUAL ROLE IN S-PHASE PROGRESSION AND AT A CELL-CYCLE CHECKPOINT
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DOI：
10.1073/pnas.92.25.11791
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发表时间：
1995-12-05
影响因子：
11.1
通讯作者：
SUGINO, A
中科院分区：
文献类型：
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作者：
ARAKI, H;LEEM, SH;SUGINO, A
DPB11是一种抑制酿酒酵母DNA聚合酶II（epsilon）两个基本亚基突变的基因，该基因由POL2和DPB2编码，已被分离到多拷贝质粒上。DPB11基因的核苷酸序列显示一个开放的阅读框，预测一个87-kDa的蛋白。该蛋白与具有细胞周期检查点功能的裂糖菌rad4(+)/cut5（+）基因产物同源。破坏DPB11是致命的，这表明DPB11对细胞增殖至关重要。在热敏型dpb11-1突变细胞中，在不允许的温度下，s期进展是有缺陷的，随后是细胞分裂，染色体分离不均匀，并伴有活力丧失。在所有温度下，Dpb11-1对dpb2-1、pol2-11和po12-18突变中的任何一种都具有合成致死性。此外，dpb11细胞对羟基脲、甲磺酸甲酯和紫外线照射敏感。这些结果强烈表明，Dpb11是染色体DNA复制过程中DNA聚合酶II复合体的一部分，并且在细胞周期的S期也在检查点途径中起作用，以感知停滞的DNA复制。
DPB11, a gene that suppresses mutations in two essential subunits of Saccharomyces cerevisiae DNA polymerase II(epsilon) encoded by POL2 and DPB2, was isolated on a multicopy plasmid. The nucleotide sequence of the DPB11 gene revealed an open reading frame predicting an 87-kDa protein. This protein is homologous to the Schizosaccharomyces pombe rad4(+)/cut5(+) gene product that has a cell cycle checkpoint function. Disruption of DPB11 is lethal, indicating that DPB11 is essential for cell proliferation. In thermosensitive dpb11-1 mutant cells, S-phase progression is defective at the nonpermissive temperature, followed by cell division with unequal chromosomal segregation accompanied by loss of viability. dpb11-1 is synthetic lethal with any one of the dpb2-1, pol2-11, andpo12-18 mutations at all temperatures. Moreover, dpb11 cells are sensitive to hydroxyurea, methyl methanesulfonate, and UV irradiation. These results strongly suggest that Dpb11 is a part of the DNA polymerase II complex during chromosomal DNA replication and also acts in a checkpoint pathway during the S phase of the cell cycle to sense stalled DNA replication.