Combined haploinsufficiency and genetic control of the G2/M checkpoint in irradiated cells.
Combined haploinsufficiency and genetic control of the G2/M checkpoint in irradiated cells.
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DOI：
10.1667/rr2875.1
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发表时间：
2012-06
影响因子：
3.4
通讯作者：
Hall EJ
中科院分区：
文献类型：
--
作者：
Young EF;Smilenov LB;Lieberman HB;Hall EJ
当细胞暴露于足以引起染色体畸变的辐射剂量时，它们在G2/M检查点被阻止，促进DNA修复。检查点控制基因的缺陷可以赋予放射敏感性。在小鼠胚胎成纤维细胞中，在0至12小时的时间过程中，在剂量范围为10 m戈伊至5.0戈伊的γ辐射下监测阻滞动力学。我们在低于100 mGy的剂量下没有观察到显著的检查点参与。检查点只有在大多数细胞要么注定发生有丝分裂灾难，要么生殖死亡的剂量下才被完全激活。检查点功能被消除的ATM空细胞没有表现出强的阻滞。令人惊讶的是，ATM单独或与其他放射抗性基因组合的单倍不足并没有改变检查点激活。我们以前已经表明，几个辐射抗性基因的单倍不足赋予中间表型的几个终点，包括细胞凋亡，转化和生存。这些发现表明，检查点控制并不有助于这些中间表型，并且与低剂量相比，不同的生物过程可以在高剂量下被激活。
When cells are exposed to a dose of radiation large enough to cause chromosome aberrations, they become arrested at the G2/M checkpoint, facilitating DNA repair. Defects in checkpoint control genes can impart radiosensitivity. Arrest kinetics were monitored in mouse embryo fibroblasts at doses ranging from 10 mGy to 5.0 Gy of γ radiation over a time course of 0 to 12 h. We observe no significant checkpoint engagement at doses below 100 mGy. The checkpoint is only fully activated at doses where most of the cells are either bound for mitotic catastrophe or are reproductively dead. Atm null cells with ablated checkpoint function exhibited no robust arrest. Surprisingly, haploinsufficiency for ATM alone or in combination with other radioresistance genes did not alter checkpoint activation. We have shown previously that haploinsufficiency for several radioresistance genes imparts intermediate phenotypes for several end points including apoptosis, transformation and survival. These findings suggest that checkpoint control does not contribute toward these intermediate phenotypes and that different biological processes can be activated at high doses compared to low doses.
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DOI：
10.1073/pnas.201167798
发表时间：
2001-09-25
影响因子：
11.1
作者：
Kwabi-Addo, B;Giri, D;Ittmann, M
通讯作者：
Ittmann, M
影响因子：
3.4
作者：
Ding, LH;Shingyoji, M;Chen, DJ
通讯作者：
Chen, DJ
DOI：
10.1016/j.asr.2004.12.032
发表时间：
2005-01-01
期刊：
SPACE LIFE SCIENCES: GROUND-BASED IRON-ION BIOLOGY AND PHYSICS, INCLUDING SHIELDING
影响因子：
--
作者：
Hall, EJ;Brenner, DJ;Smilenov, L
通讯作者：
Smilenov, L
影响因子：
64.5
作者：
Barlow, C;Hirotsune, S;WynshawBoris, A
通讯作者：
WynshawBoris, A
影响因子：
56.9
作者：
Di Cristofano, A;Kotsi, P;Pandolfi, PP
通讯作者：
Pandolfi, PP