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首页> 外文期刊>Oncogene >Chk2 is required for optimal mitotic delay in response to irradiation-induced DNA damage incurred in G2 phase
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Chk2 is required for optimal mitotic delay in response to irradiation-induced DNA damage incurred in G2 phase

机译：Chk2是响应G2期在辐照引起的DNA损伤时最佳的有丝分裂延迟所必需的

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Whether Chk2 contributes to DNA damage-induced arrest in G2 has been controversial. To investigate this issue further, we generated Chk2-deficient DT40 B-lymphoma cells by gene targeting and compared their cell cycle response to ionizing radiation (IR) with wild-type (WT) and isogenic Chk1-deficient counterparts. After moderate doses of IR (4?Gy), we find that Chk2?/? cells which are in G1 or S phase at the time of irradiation arrest efficiently in G2. In contrast, Chk2?/? cells which are in G2 when DNA damage is incurred exhibit an impaired mitotic delay compared to WT, with the result that cells enter mitosis with damaged DNA as judged by the presence of numerous γ-H2AX foci on condensed chromosomes. Impaired G2 delay as the result of Chk2 deficiency can be detected at very low doses of radiation (0.1?Gy), and may allow division with spontaneous DNA damage, since a higher proportion of mitotic Chk2?/? cells bear spontaneous γ-H2AX foci and damaged chromosomes during unperturbed growth compared to WT. The contribution of Chk2 to G2/M delay is epistatic to that of Chk1, since Chk1?/? cells exhibit no measurable mitotic delay at any radiation dose tested. We suggest that this function of Chk2 could contribute to tumour suppression, since cell division with low levels of spontaneous damage is likely to promote genetic instability and thus carcinogenesis.
机译：Chk2是否有助于DNA损伤诱导的G2阻滞一直存在争议。为了进一步研究这个问题，我们通过基因定位产生了Chk2缺陷型DT40 B淋巴瘤细胞，并将其对电离辐射（IR）的细胞周期响应与野生型（WT）和等基因的Chk1缺陷对应物进行了比较。适量的IR（4？Gy）后，我们发现Chk2？/？是多少？照射时处于G1或S期的细胞有效地停滞在G2中。相反，Chk2？/？与WT相比，当发生DNA损伤时位于G2的细胞表现出受损的有丝分裂延迟，其结果是，通过浓缩染色体上存在大量γ-H2AX病灶可以判断出细胞进入了DNA受损的有丝分裂状态。由于Chk2缺乏导致的G2延迟受损，可以在非常低的辐射剂量下（0.1？Gy）检测到，并且由于有丝分裂的Chk2？/？比例更高，可能导致分裂并自发性DNA损伤。与WT相比，细胞在不受干扰的生长过程中具有自发的γ-H2AX病灶和受损的染色体。由于Chk1β/β，Chk2对G2 / M延迟的贡献与Chk1相比是上位的。在任何测试的辐射剂量下，细胞都没有可测量的有丝分裂延迟。我们建议Chk2的这种功能可能有助于抑制肿瘤，因为具有低水平自发性损伤的细胞分裂可能促进遗传不稳定，从而促进癌变。

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