Homology-Directed Repair is Required for the Development of Radioresistance during S Phase: Interplay between Double-Strand Break Repair and Checkpoint Response
Homology-Directed Repair is Required for the Development of Radioresistance during S Phase: Interplay between Double-Strand Break Repair and Checkpoint Response
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DOI：
10.1667/rr0751.1
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发表时间：
2007
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影响因子：
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通讯作者：
P. Tamulevicius;Minli Wang;G. Iliakis
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文献类型：
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作者：
P. Tamulevicius;Minli Wang;G. Iliakis
Tamulevicius， P., Wang， M.和Iliakis， G.同源性定向修复是S期辐射耐药发展所必需的：双链断裂修复和检查点反应之间的相互作用。Radiat。Res. 167, 1 - 11（2007）。真核细胞中普遍存在的s期依赖性辐射杀伤抗性，在涉及同源重组修复DNA双链断裂（DSBs）的基因缺陷的辐射敏感突变体（同源重组修复：HRR）中不存在。这意味着，这是第一次，一个具体的DNA修复过程在一个特定的细胞周期阶段的辐射敏感性。细胞周期依赖的辐射敏感性波动反映了一种基本的、有充分证据的放射生物学现象，该现象仍有待详细的分子表征。潜在的机制可能结合了DNA修复和细胞周期调节的各个方面。这两个领域的进展使我们能够在细胞周期中首次剖析DSB修复和DNA损伤检查点反应之间的分子相互作用及其对细胞存活的贡献。在这里，我们回顾了有关该主题的现有文献，推测了这些信息对我们理解细胞对DNA损伤反应的影响，并讨论了未来的研究方向。一个努力作出整合辐射作用的相关现象，如低剂量辐射敏感性和G2测定在这个方案。
Abstract Tamulevicius, P., Wang, M. and Iliakis, G. Homology-Directed Repair is Required for the Development of Radioresistance during S Phase: Interplay between Double-Strand Break Repair and Checkpoint Response. Radiat. Res. 167, 1– 11 (2007). The S-phase-dependent radioresistance to killing uniformly seen in eukaryotic cells is absent in radiosensitive mutants with defects in genes involved in the repair of DNA double-strand breaks (DSBs) by homologous recombination (homologous recombination repair: HRR). This implicates, for the first time, a concrete DNA repair process in the radiosensitivity of a specific cell cycle phase. The cell cycle-dependent fluctuations in radiosensitivity reflect a fundamental and well-documented radiobiological phenomenon that still awaits a detailed molecular characterization. The underlying mechanisms are likely to combine aspects of DNA repair and cell cycle regulation. Advances in both fields allow a first dissection in the cell cycle of the molecular interplay between DSB repair and DNA damage checkpoint response and its contribution to cell survival. Here we review the available literature on the topic, speculate on the ramifications of this information for our understanding of cellular responses to DNA damage, and discuss future directions in research. An effort is made to integrate relevant phenomena of radiation action, such as low-dose radiosensitivity and the G2 assay in this scheme.