Implication of the VRK1 chromatin kinase in the signaling responses to DNA damage: a therapeutic target?
Implication of the VRK1 chromatin kinase in the signaling responses to DNA damage: a therapeutic target?
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DOI：
10.1007/s00018-018-2811-2
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发表时间：
2018-07
期刊：
影响因子：
--
通讯作者：
Lazo PA
中科院分区：
文献类型：
--
作者：
Campillo-Marcos I;Lazo PA
DNA损伤导致染色质的局部变形，从而触发参与特定DNA修复机制的顺序过程。修复反应的启动需要一种活性可受组蛋白调节的蛋白质的参与。激酶是调节和协调局部改变的染色质与导致识别病变类型和特异性DNA损伤反应（DDR）中所需的顺序步骤的反应起始信号之间的连接的候选者。这种起始激酶必须位于染色质中，并且独立于DNA损伤的类型被激活。我们审查的贡献，丝氨酸-苏氨酸牛痘相关激酶1（VRK 1）染色质激酶作为一个新的球员在DNA损伤反应的信号，在染色质和细胞水平，其潜力作为一个新的治疗靶点在肿瘤学。VRK 1参与调节组蛋白修饰，如组蛋白磷酸化和乙酰化，并参与DDR诱导的γ H2 AX、NBS 1和53 BP 1灶的形成。通过化疗或放疗诱导DNA损伤是癌症治疗的主要手段。因此，新的治疗方法可以靶向参与DDR调节的蛋白质，而不是直接引起DNA损伤。
DNA damage causes a local distortion of chromatin that triggers the sequential processes that participate in specific DNA repair mechanisms. This initiation of the repair response requires the involvement of a protein whose activity can be regulated by histones. Kinases are candidates to regulate and coordinate the connection between a locally altered chromatin and the response initiating signals that lead to identification of the type of lesion and the sequential steps required in specific DNA damage responses (DDR). This initiating kinase must be located in chromatin, and be activated independently of the type of DNA damage. We review the contribution of the Ser-Thr vaccinia-related kinase 1 (VRK1) chromatin kinase as a new player in the signaling of DNA damage responses, at chromatin and cellular levels, and its potential as a new therapeutic target in oncology. VRK1 is involved in the regulation of histone modifications, such as histone phosphorylation and acetylation, and in the formation of γH2AX, NBS1 and 53BP1 foci induced in DDR. Induction of DNA damage by chemotherapy or radiation is a mainstay of cancer treatment. Therefore, novel treatments can be targeted to proteins implicated in the regulation of DDR, rather than by directly causing DNA damage.
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影响因子：
19
作者：
Ceccaldi R;Rondinelli B;D'Andrea AD
通讯作者：
D'Andrea AD
影响因子：
16
作者：
Downs, JA;Allard, S;Côté, J
通讯作者：
Côté, J
DOI：
10.1073/pnas.0708800104
发表时间：
2007-12-18
影响因子：
11.1
作者：
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通讯作者：
Knapp, Stefan
影响因子：
16
作者：
Ciccia A;Elledge SJ
通讯作者：
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影响因子：
5.3
作者：
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通讯作者：
Lowe, SW