MU2 and HP1a regulate the recognition of double strand breaks in Drosophila melanogaster.
MU2 and HP1a regulate the recognition of double strand breaks in Drosophila melanogaster.
复制标题
DOI：
10.1371/journal.pone.0025439
复制
发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Mason JM
中科院分区：
文献类型：
--
作者：
Dronamraju R;Mason JM
染色质结构调节DNA双链断裂的识别和修复的动力学;开放的染色质增强DNA损伤反应因子的募集，而紧凑的染色质对辐射诱导的修复灶的组装是难治的。MU 2是人MDC 1的直向同源物，是电离辐射诱导的修复灶的支架，是黑腹果蝇中广泛分布的染色体蛋白，在辐射后移动到DNA修复灶。在这里，我们使用酵母2杂交筛选和免疫共沉淀，MU 2结合未处理细胞中异染色质蛋白HP 1的chromoshadow结构域。我们问HP 1在DNA损伤后修复灶的形成和细胞周期控制中起什么作用。照射后，修复灶在异染色质中形成，但以HP 1依赖的方式分流到异染色质区域的边缘，这表明了区室化修复。然而，在折叠的复制叉处形成的羟基脲诱导的修复灶仍保留在异染色质区室中。HP 1a在照射后的椎间盘细胞中的缺失增加了细胞凋亡并破坏了G2/M期阻滞。此外，有丝分裂期照射的细胞比间期照射的细胞产生更多更亮的修复灶。因此，MU 2和HP 1a之间的相互作用是动态的，并且在DNA断裂识别和修复期间在常染色质和异染色质中可能是不同的。
Chromatin structure regulates the dynamics of the recognition and repair of DNA double strand breaks; open chromatin enhances the recruitment of DNA damage response factors, while compact chromatin is refractory to the assembly of radiation-induced repair foci. MU2, an orthologue of human MDC1, a scaffold for ionizing radiation-induced repair foci, is a widely distributed chromosomal protein in Drosophila melanogaster that moves to DNA repair foci after irradiation. Here we show using yeast 2 hybrid screens and co-immunoprecipitation that MU2 binds the chromoshadow domain of the heterochromatin protein HP1 in untreated cells. We asked what role HP1 plays in the formation of repair foci and cell cycle control in response to DNA damage. After irradiation repair foci form in heterochromatin but are shunted to the edge of heterochromatic regions an HP1-dependent manner, suggesting compartmentalized repair. Hydroxyurea-induced repair foci that form at collapsed replication forks, however, remain in the heterochromatic compartment. HP1a depletion in irradiated imaginal disc cells increases apoptosis and disrupts G2/M arrest. Further, cells irradiated in mitosis produced more and brighter repair foci than to cells irradiated during interphase. Thus, the interplay between MU2 and HP1a is dynamic and may be different in euchromatin and heterochromatin during DNA break recognition and repair.
登录
查看更多内容
DOI：
10.1073/pnas.110149597
发表时间：
2000-06-06
影响因子：
11.1
作者：
Clemens, JC;Worby, CA;Dixon, JE
通讯作者：
Dixon, JE
影响因子：
4.3
作者：
Ayoub, Nabieh;Jeyasekharan, Anand D.;Venkitaraman, Ashok R.
通讯作者：
Venkitaraman, Ashok R.
影响因子：
11.4
作者：
BIESSMANN, H;MASON, JM
通讯作者：
MASON, JM
影响因子：
64.8
作者：
Ayoub, Nabieh;Jeyasekharan, Anand D.;Venkitaraman, Ashok R.
通讯作者：
Venkitaraman, Ashok R.
DOI：
10.1073/pnas.0813063106
发表时间：
2009-06-02
影响因子：
11.1
作者：
Fischer, Tamas;Cui, Bowen;Grewal, Shiv I. S.
通讯作者：
Grewal, Shiv I. S.