MITOSIS COUPLING TO COMPLETION OF DNA REPLICATION

染色体特别容易受到遗传损伤，而 它们正在被复制。如果DNA受损，或者没有 当有足够的核苷酸时，复制过程就会停止 问题已得到纠正。这不太可能是由于身体上的 阻止到DNA复制，相当复杂的机制，涉及 细胞周期调控和DNA修复确保S期停滞和 复苏以有序的方式进行。通过防止遗传 复制过程中的变化，S阶段的机制 逮捕和康复在预防癌症中发挥着重要作用。 此外，由于S相的缓蚀剂经常用于 化疗，了解S停滞的细胞学基础 而康复对健康具有相当大的相关性。 我们一直在研究5阶段的逮捕和恢复使用 裂殖酵母，裂殖酵母。喜欢的越多 研究较多的酵母菌有酿酒酵母、金黄色葡萄球菌 使用一系列强大的分子和 基因技术。我们已经鉴定出有缺陷的突变体 通过筛选经历了5个阶段的突变来阻止和恢复 羟基脲(HU)治疗后的异常有丝分裂 抑制DNA合成。我们已经确定的两个基因是 与癌症易感综合征中的人类基因突变有关。Rd3+ 是S期停搏所必需的，与atm基因有关， 在共济失调-毛细血管扩张症(A-T)患者中缺乏。 HUS2+是从S停搏中恢复所必需的，与 BLM，该基因在患有布卢姆斯综合征患者中发生突变 (B)。A-T和BS患者表现出一系列复杂的症状， 包括一系列癌症风险的显著增加。至 更好地了解预防癌症的细胞过程，我们 建议分析S所需的Rd3+、Hs2+等基因-- 阶段性停止和恢复。

Chromosomes are particularly vulnerable to genetic damage while they are being replicated. If DNA is damaged, or if there are not enough nucleotides, the process of replication is halted while problems are corrected. This is unlikely to be due to a physical block to DNA replication, rather complex mechanisms involving cell cycle control and DNA repair ensure that S-phase arrest and recovery take place in an orderly fashion. By preventing genetic changes during replication, the mechanisms underlying S-phase arrest and recovery play an important role in preventing cancer. Moreover, since inhibitors of S-phase are frequently used in chemotherapy, understanding the cellular basis of S-phase arrest and recovery is of considerable health relevance. We have been studying 5-phase arrest and recovery using the fission yeast, Schizosaccharomyces pombe. Like the more commonly studied yeast, Saccharomyces cerevisiae, S. pombe can be conveniently studied using a range of powerful molecular and genetic techniques. We have identified mutants that have defects in 5-phase arrest and recovery by screening for mutants that undergo abnormal mitoses upon treatment with hydroxyurea (HU), an inhibitor DNA synthesis. Two of the genes we have identified are related to human genes mutated in cancer-prone syndromes. Rad3+ is required for S-phase arrest and is related to the ATM gene, deficient in patients suffering from Ataxia-Telangiectasia (A-T). hus2+ is required for recovery from S-phase arrest and is related to BLM, the gene mutated in patients afflicted with Blooms Syndrome (BS). A-T and BS patients display a range of complex symptoms, including a significantly increased risk for a range of cancers. To better understand the cellular processes preventing cancer, we are proposing to analyze rad3+, hus2+ and other genes required for S- phase arrest and recovery.