Dbf4 recruitment by forkhead transcription factors defines an upstream rate-limiting step in determining origin firing timing.
Dbf4 recruitment by forkhead transcription factors defines an upstream rate-limiting step in determining origin firing timing.
复制标题
叉头转录因子招募 Dbf4 定义了确定起始激发时间的上游限速步骤
DOI：
10.1101/gad.306571.117
复制
发表时间：
2017-12-01
影响因子：
10.5
通讯作者：
Lou H
中科院分区：
文献类型：
--
作者：
Fang D;Lengronne A;Shi D;Forey R;Skrzypczak M;Ginalski K;Yan C;Wang X;Cao Q;Pasero P;Lou H
Fang等人表明Dbf4通过与叉头转录因子Fkh1和Fkh2的相互作用在早期起源中富集。Dbf4直接与Sld3相互作用，促进下游限制因子的募集。真核生物染色体复制的启动遵循时空程序。目前的模型表明，复制起点竞争有限的启动因子池。然而，这些限制因素如何优先被招募到早期起源仍有待回答。在这里，我们报告Dbf4是丰富的早期起源，通过其与叉头转录因子Fkh1和Fkh2的相互作用。这种相互作用是由Dbf 4 C末端介导的，并在体外成功地重建。相互作用缺陷突变体dbf 4 ΔC在起源激发方面模仿fkh等位基因。值得注意的是，全基因组复制谱显示，Fkh1的DNA结合结构域（DBD）与Dbf4的直接融合恢复了Fkh1依赖的起始点发射，但特异性地干扰了着丝粒周围起始点的激活。此外，Dbf4直接与Sld3相互作用，并促进下游限制因子的募集。这些数据表明，Fkh1的目标Dbf4的一个子集的noncentromeric的起点，以促进早期复制的方式，这是令人想起的招聘Dbf4的centromeric的起源由Ctf19。
Fang et al. show that Dbf4 is enriched at early origins through its interaction with forkhead transcription factors Fkh1 and Fkh2. Dbf4 interacts directly with Sld3 and promotes the recruitment of downstream limiting factors. Initiation of eukaryotic chromosome replication follows a spatiotemporal program. The current model suggests that replication origins compete for a limited pool of initiation factors. However, it remains to be answered how these limiting factors are preferentially recruited to early origins. Here, we report that Dbf4 is enriched at early origins through its interaction with forkhead transcription factors Fkh1 and Fkh2. This interaction is mediated by the Dbf4 C terminus and was successfully reconstituted in vitro. An interaction-defective mutant, dbf4ΔC, phenocopies fkh alleles in terms of origin firing. Remarkably, genome-wide replication profiles reveal that the direct fusion of the DNA-binding domain (DBD) of Fkh1 to Dbf4 restores the Fkh-dependent origin firing but interferes specifically with the pericentromeric origin activation. Furthermore, Dbf4 interacts directly with Sld3 and promotes the recruitment of downstream limiting factors. These data suggest that Fkh1 targets Dbf4 to a subset of noncentromeric origins to promote early replication in a manner that is reminiscent of the recruitment of Dbf4 to pericentromeric origins by Ctf19.
登录
查看更多内容
影响因子：
4.3
作者：
Jones, Darryl R.;Prasad, Ajai A.;Duncker, Bernard P.
通讯作者：
Duncker, Bernard P.
影响因子：
64.5
作者：
Knott SR;Peace JM;Ostrow AZ;Gan Y;Rex AE;Viggiani CJ;Tavaré S;Aparicio OM
通讯作者：
Aparicio OM
影响因子：
11.4
作者：
Kamimura, Y;Tak, YS;Araki, H
通讯作者：
Araki, H
影响因子：
11.4
作者：
Kanemaki, Masato;Labib, Karim
通讯作者：
Labib, Karim
影响因子：
3.3
作者：
Harkins, Victoria;Gabrielse, Carrie;Weinreich, Michael
通讯作者：
Weinreich, Michael