The DNA damage response: making it safe to play with knives.

The DNA damage response: making it safe to play with knives.
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DOI:
10.1016/j.molcel.2010.09.019
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发表时间:
2010-10-22
期刊:
影响因子:
16
通讯作者:
Elledge SJ
Elledge SJ
中科院分区:
生物学1区
文献类型:
--
作者:
Ciccia A;Elledge SJ

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对我们遗传物质的损害是对我们忠实地将遗传信息传递给后代的能力以及我们自己生存的持续威胁。为了应对这些威胁,真核生物进化出了DNA损伤反应(DDR)。DDR是一种复杂的信号转导途径,能够感知DNA损伤并将此信息传递给细胞,以影响细胞对DNA损伤的反应。细胞拥有能够重塑和修复DNA的酶工具库,然而,它们的活性必须以时间、空间和DNA损伤适当的方式严格调节,以优化修复并防止正常细胞过程中DNA结构中不必要的和潜在有害的改变。本文将重点关注DDR如何控制DNA修复以及哺乳动物这些关键调节功能缺陷的表型后果。
Damage to our genetic material is an ongoing threat to both our ability to faithfully transmit genetic information to our offspring as well as our own survival. To respond to these threats, eukaryotes have evolved the DNA Damage Response (DDR). The DDR is a complex signal transduction pathway that has the ability to sense DNA damage and transduce this information to the cell to influence cellular responses to DNA damage. Cells possess an arsenal of enzymatic tools capable of remodeling and repairing DNA, however, their activities must be tightly regulated in a temporal, spatial and DNA lesion-appropriate fashion to optimize repair and prevent unnecessary and potentially deleterious alterations in the structure of DNA during normal cellular processes. This review will focus on how the DDR controls DNA repair and the phenotypic consequences of defects in these critical regulatory functions in mammals.
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