The Fkh1 Forkhead associated domain promotes ORC binding to a subset of DNA replication origins in budding yeast.
The Fkh1 Forkhead associated domain promotes ORC binding to a subset of DNA replication origins in budding yeast.
复制标题
DOI：
10.1093/nar/gkab450
复制
发表时间：
2021-10-11
影响因子：
14.9
通讯作者：
Fox CA
中科院分区：
文献类型：
--
作者：
Hoggard T;Hollatz AJ;Cherney RE;Seman MR;Fox CA
真核生物DNA复制的先驱事件是起始转录复合物（ORC）与染色体DNA的结合。ORC-DNA复合物指导起源的形成，DNA合成起始的特定染色体区域。在所有真核生物中，染色质的不完全理解的特征促进ORC-DNA结合。在这里，我们发现了Fkh 1（叉头同源物）蛋白及其叉头相关（FHA）结构域在促进ORC-起源结合和起源活性在酿酒酵母起源的一个子集中的作用。几个FHA依赖性来源需要一个独特的Fkh 1结合位点，位于其ORC位点的5′端和近端（5′-FKH-T位点）。遗传学和分子生物学实验证明，Fkh 1-FHA结构域直接通过Fkh 1与该5′ FKH-T位点的结合促进了起源活性。在两个相关来源内的核苷酸取代增强了它们的ORC-DNA亲和力，绕过了对它们的5′ FKH-T位点和Fkh 1-FHA结构域的要求。值得注意的是，ChIPSeq对ORC-来源结合的评估提供了证据，表明该机制与约25%的酵母来源相关。因此，保守的细胞周期转录因子Fkh 1的FHA结构域增强了酵母在ORC-起源结合水平上的起源选择。
The pioneer event in eukaryotic DNA replication is binding of chromosomal DNA by the origin recognitioncomplex (ORC). The ORC-DNA complex directs the formation of origins, the specific chromosomal regions where DNA synthesis initiates. In all eukaryotes, incompletely understood features of chromatin promote ORC-DNA binding. Here, we uncover a role for the Fkh1 (Forkhead homolog) protein and its forkhead associated (FHA) domain in promoting ORC-origin binding and origin activity at a subset of origins in Saccharomyces cerevisiae. Several of the FHA-dependent origins examined required a distinct Fkh1 binding site located 5′ of and proximal to their ORC sites (5′-FKH-T site). Genetic and molecular experiments provided evidence that the Fkh1-FHA domain promoted origin activity directly through Fkh1 binding to this 5′ FKH-T site. Nucleotide substitutions within two relevant origins that enhanced their ORC-DNA affinity bypassed the requirement for their 5′ FKH-T sites and for the Fkh1-FHA domain. Significantly, assessment of ORC-origin binding by ChIPSeq provided evidence that this mechanism was relevant at ∼25% of yeast origins. Thus, the FHA domain of the conserved cell-cycle transcription factor Fkh1 enhanced origin selection in yeast at the level of ORC-origin binding.
登录
查看更多内容
影响因子：
3.3
作者：
Bell SP;Labib K
通讯作者：
Labib K
影响因子：
16.6
作者：
Hu Y;Tareen A;Sheu YJ;Ireland WT;Speck C;Li H;Joshua-Tor L;Kinney JB;Stillman B
通讯作者：
Stillman B
影响因子：
16
作者：
McGuffee, Sean R.;Smith, Duncan J.;Whitehouse, Iestyn
通讯作者：
Whitehouse, Iestyn
影响因子：
21.3
作者：
Feng, Wenyi;Collingwood, David;Boeck, Max E;Fox, Lindsay A;Alvino, Gina M;Fangman, Walton L;Raghuraman, Mosur K;Brewer, Bonita J
通讯作者：
Brewer, Bonita J
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
影响因子：
10.5
作者：
Fang D;Lengronne A;Shi D;Forey R;Skrzypczak M;Ginalski K;Yan C;Wang X;Cao Q;Pasero P;Lou H
通讯作者：
Lou H