NEST, Scuola Normale Superiore and Istituto Nanoscienze-CNR, Laboratorio di Biologia Molecolare, Scuola Normale Superiore, Pisa, Italy.
Nucleic Acids Res. 2010 Dec;38(22):8105-19. doi: 10.1093/nar/gkq688. Epub 2010 Aug 6.
Recent evidence points to homeotic proteins as actors in the crosstalk between development and DNA replication. The present work demonstrates that HOXC13, previously identified as a new member of human DNA replicative complexes, is a stable component of early replicating chromatin in living cells: it displays a slow nuclear dynamics due to its anchoring to the DNA minor groove via the arginine-5 residue of the homeodomain. HOXC13 binds in vivo to the lamin B2 origin in a cell-cycle-dependent manner consistent with origin function; the interaction maps with nucleotide precision within the replicative complex. HOXC13 displays in vitro affinity for other replicative complex proteins; it interacts also in vivo with the same proteins in a cell-cycle-dependent fashion. Chromatin-structure modifying treatments, disturbing origin function, reduce also HOXC13-origin interaction. The described interactions are not restricted to a single origin nor to a single homeotic protein (also HOXC10 binds the lamin B2 origin in vivo). Thus, HOX complexes probably contribute in a general, structure-dependent manner, to origin identification and assembly of replicative complexes thereon, in presence of specific chromatin configurations.
最近的证据表明同源蛋白是发育和 DNA 复制之间串扰的参与者。本研究表明，HOXC13 先前被鉴定为人类 DNA 复制复合物的新成员，是活细胞中早期复制染色质的稳定组成部分：由于其通过同源域的精氨酸 5 残基锚定在 DNA 小沟中，因此显示出缓慢的核动力学。HOXC13 以细胞周期依赖性方式与 lamin B2 起始点结合，与起始点功能一致；相互作用以核苷酸精度映射到复制复合物内。HOXC13 在体外对其他复制复合物蛋白具有亲和力；它也以细胞周期依赖性方式与体内相同的蛋白质相互作用。染色质结构修饰处理，扰乱起始点功能，也降低了 HOXC13-起始点的相互作用。所描述的相互作用不仅限于单个起始点，也不限于单个同源蛋白（HOXC10 也在体内与 lamin B2 起始点结合）。因此，HOX 复合物可能以普遍的、结构依赖性的方式，在存在特定染色质构型的情况下，有助于识别起始点并在其上组装复制复合物。
