Details and concerns regarding the G2/M DNA damage checkpoint in budding yeast.
Details and concerns regarding the G2/M DNA damage checkpoint in budding yeast.
复制标题
有关芽殖酵母中 G2/M DNA 损伤检查点的详细信息和担忧。
DOI：
10.1101/sqb.2000.65.433
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发表时间：
2000
期刊：
影响因子：
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通讯作者：
Sundareshan,P
中科院分区：
文献类型：
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作者：
Weinert,T;Little,E;Shanks,L;Admire,A;Gardner,R;Putnam,C;Michelson,R;Nyberg,K;Sundareshan,P
这些维修中的其他角色是什么？一个作用可能是通过基因表达；例如，至少一些修复基因的转录诱导需要许多检查点基因(Weinert 1998a)。此外，最近的两份报告表明，检查点基因可能通过调节修复/重组装置在重组途径的调控中发挥作用(Grushcoo等人。1999)或通过修复蛋白的直接磷酸化(Bashkirov等人。2000)。此外，一些检查点基因在DNA降解中仍扮演着神秘的角色，可能会影响DNA修复(Lydall和Weinert 1995)。因此，对于每个检查点突变表型，我们需要询问细胞周期进程或其他功能中缺陷的相关性。为什么这些其他功能很重要，我们如何研究它们？首先，在某些情况下，这些“第二”功能可能与细胞周期的延迟一样重要，甚至更重要(例如，参见基因组不稳定一节)。此外，为了最终操纵癌症治疗的检查点途径，必须更全面地了解许多角色。我们应该如何理解多个角色中的每一个对细胞损伤反应的影响？一种概念上简单的方法是分离相应基因中的功能分离等位基因，这是一种成功地在生物学的许多领域理解多功能基因的方法(曹等人。1997年；巴蒂等人。1998年；Sekiya-Kawasaki et al.1998)，我们目前正在尝试使用Mec1和RAD9。一些检查点基因中的功能分离突变提供了信息(例如，Uchiyama等人)。1997年；Sun等人。1998)，我们认为这些等位基因可能被证明在区分无数的活动中是重要的。
What are these other roles in repair? One role is likely through gene expression; for example, many checkpoint genes are required for transcriptional induction of at least some repair genes (Weinert 1998a). In addition, two recent reports indicate that checkpoint genes have roles in regulation of recombination pathways, perhaps through regulation of the repair/recombination apparatus (Grushcow et al. 1999) or through direct phosphorylation of repair proteins (Bashkirov et al. 2000). In addition, some checkpoint genes have a still-enigmatic role in DNA degradation that might influence DNA repair (Lydall and Weinert 1995).For each checkpoint mutant phenotype, we thus need to ask the relevance of defects in cell cycle progression or in other functions. Why are these other functions important, and how do we study them? First, these “second” functions may in some instances be as important or even more so than delays in the cell cycle (see section on genomic instability for an example). In addition, to eventually manipulate checkpoint pathways for cancer therapy, the many roles must be more completely understood. How should we try to understand the impact on the cell’s response to damage by each of the multiple roles? A conceptually simple way is to isolate separation-of-function alleles in the corresponding genes, an approach successful to understanding multifunctional genes in many areas of biology (Cao et al. 1997; Butty et al. 1998; Sekiya-Kawasaki et al. 1998), and one we are currently attempting with MEC1 and RAD9. Separation-of-function mutations in some checkpoint genes have been informative (see, eg, Uchiyama et al. 1997; Sun et al. 1998), and we think that such alleles may prove to be important in sorting out the myriad of activities.