SirA inhibits the essential DnaA:DnaD interaction to block helicase recruitment during Bacillus subtilis sporulation.
SirA inhibits the essential DnaA:DnaD interaction to block helicase recruitment during Bacillus subtilis sporulation.
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DOI：
10.1093/nar/gkac1060
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发表时间：
2023-05-22
影响因子：
14.9
通讯作者：
Murray, Heath
中科院分区：
文献类型：
--
作者：
Winterhalter, Charles;Stevens, Daniel;Fenyk, Stepan;Pelliciari, Simone;Marchand, Elie;Soultanas, Panos;Ilangovan, Aravindan;Murray, Heath
从染色体起点的双向DNA复制需要两个解旋酶的不对称加载，每个复制体一个。我们对细菌染色体起源处解旋酶加载的分子机制的理解是不完整的。在这里，我们报告了在模式生物枯草芽孢杆菌中定向解旋酶招募的积极和消极机制。必需的起始蛋白DnaD的系统表征揭示了同源寡聚化所需的不同蛋白质界面，与主起始蛋白DnaA的相互作用，以及与解旋酶共装载蛋白DnaB的相互作用。根据DnaD的这些特性，我们继续发现发育中表达的DNA复制起始阻遏物SirA阻断了DnaD和DnaA之间的相互作用，从而限制了解旋酶在孢子形成过程中从起点的募集，以抑制进一步的起始事件。这些结果推进了我们对B中DNA复制起始机制的理解。枯草杆菌，以及指导寻找基本的细胞活性，以靶向抗微生物药物设计。
Bidirectional DNA replication from a chromosome origin requires the asymmetric loading of two helicases, one for each replisome. Our understanding of the molecular mechanisms underpinning helicase loading at bacterial chromosome origins is incomplete. Here we report both positive and negative mechanisms for directing helicase recruitment in the model organism Bacillus subtilis. Systematic characterization of the essential initiation protein DnaD revealed distinct protein interfaces required for homo-oligomerization, interaction with the master initiator protein DnaA, and interaction with the helicase co-loader protein DnaB. Informed by these properties of DnaD, we went on to find that the developmentally expressed repressor of DNA replication initiation, SirA, blocks the interaction between DnaD and DnaA, thereby restricting helicase recruitment from the origin during sporulation to inhibit further initiation events. These results advance our understanding of the mechanisms underpinning DNA replication initiation in B. subtilis, as well as guiding the search for essential cellular activities to target for antimicrobial drug design.
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通过细菌启动器拉伸的DNA促进了复制起源。
影响因子：
64.8
作者：
Duderstadt, Karl E.;Chuang, Kevin;Berger, James M.
通讯作者：
Berger, James M.
影响因子：
4.8
作者：
Abe, Yoshito;Jo, Takaaki;Ueda, Tadashi
通讯作者：
Ueda, Tadashi
影响因子：
14.9
作者：
Collier C;Machón C;Briggs GS;Smits WK;Soultanas P
通讯作者：
Soultanas P
影响因子：
4.4
作者：
Chaudhuri RR;Allen AG;Owen PJ;Shalom G;Stone K;Harrison M;Burgis TA;Lockyer M;Garcia-Lara J;Foster SJ;Pleasance SJ;Peters SE;Maskell DJ;Charles IG
通讯作者：
Charles IG
影响因子：
3.6
作者：
Bruand, C;Velten, M;Polard, P
通讯作者：
Polard, P