Budding Yeast-S-phase Checkpoint Control

描述（申请人提供）基因组不稳定性是人类癌症的标志，可能涉及癌基因位点的激活突变、肿瘤抑制突变的积累和发现肿瘤抑制缺陷的特定染色体丢失。细胞周期检查点，罗三醇防止这样的基因组改变。事实上，高保真的染色体复制和传输依赖于精心设计的机制，必须在细胞周期的背景下精确控制。S期检查点是一种机制，它建立了DNA复制和有丝分裂细胞分裂的生化无关的细胞过程之间的依赖关系。功能性S期检查点确保基因组复制和分离无错误地发生，因此该检查点是防止基因组不稳定性的关键信号通路。了解S期检查点控制是增加我们对癌症病因学知识的重要目标。在临床中，肿瘤细胞的检查点完整性与设计有效的治疗方案高度相关，因为受损的检查点控制影响细胞对治疗剂的敏感性。 本申请试图理解新颖的S期检查点组件的功能。此外，我们建议专门研究我们最近发现的一种新的晚期S期检查点通路。一些，但不是全部，晚期S期检查点组件是已知的。因此，我们将研究已知的S期检查点蛋白的功能，并筛选目前未知的因素。这些因子对于维持基因组稳定性不可避免地至关重要，并且在人类中是保守的。

DESCRIPTION (provided by applicant) Genomic instability, the hallmark of human cancer, can involve activating mutations at oncogene loci, the accumulation of tumor suppressor mutations and specific chromosome losses that uncover tumor suppressor deficiencies. Cell cycle checkpoint, roritriols guard against such genome alterations. Indeed, high fidelity chromosome replication and transmission depend on elaborate mechanics that must be precisely controlled in the cell cycle context The S-phase checkpoint is a mechanism that establishes a dependence relationship between the biochemically unrelated cellular processes of DNA replication and mitotic cell division. A functional S-phase checkpoint ensures that genome duplication and segregation occur without error and this checkpoint is therefore a critical signaling pathway that guards against genome instability. Understanding S-phase checkpoint control is an important goal to increase our knowledge of cancer etiology. In the clinic, checkpoint integrity of tumor cells is highly relevant for designing effective treatment regimes, since compromised checkpoint controls affect the sensitivity of cells to therapeutic agents. This application seeks to understand the functions of novel S-phase checkpoint components. In addition, we propose to specifically investigate a novel Late S-phase Checkpoint pathway that we recently identified. Some, but not all, of the late S-phase checkpoint components are known. We will therefore investigate the functions of known S-phase checkpoint proteins and screen for currently unknown factors. These factors will inevitably be critical for the maintenance of genome stability and will be conserved in humans.