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纸质出版:2011
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程巧,厉红元,王小毅,任国胜.沉默Ku70促进PARP1、ligase3和XRCC1在DNA双链断裂染色质聚集[J].陆军军医大学学报(原第三军医大学学报),2011,33(14):1497-1501.
Cheng Qiao,Li Hongyuan,Wang Xiaoyi,Ren Guosheng.Silencing Ku70 promotes recruitment of PARP1, ligase 3 and XRCC1 at chromatin with DNA double-strand break[J].J Amry Med Univ (J Third Mil Med Univ),2011,33(14):1497-1501.
程巧,厉红元,王小毅,任国胜.沉默Ku70促进PARP1、ligase3和XRCC1在DNA双链断裂染色质聚集[J].陆军军医大学学报(原第三军医大学学报),2011,33(14):1497-1501. DOI:
Cheng Qiao,Li Hongyuan,Wang Xiaoyi,Ren Guosheng.Silencing Ku70 promotes recruitment of PARP1, ligase 3 and XRCC1 at chromatin with DNA double-strand break[J].J Amry Med Univ (J Third Mil Med Univ),2011,33(14):1497-1501. DOI:
目的 研究碱基切除修复途径(base excision repair,BER)关键因子PARP1、ligase3和XRCC1在Ku70缺失的条件下与DNA双链断裂(double-strand break,DSB)所在染色质的结合及抑制PARP1所产生的影响。 方法 采用可经药物诱导Ku70 shRNA的细胞株,以高效的DNA双链断裂诱导剂刺孢霉素calicheamicin诱导DSB。分离不同组分蛋白联合稳定同位素标记定量差异蛋白组分析法鉴定Ku70下调后在损伤染色质聚集增多的蛋白,Western blot进行验证并检测PARP1抑制剂DIQ对其染色质聚集的影响。 结果 在药物Doxy作用下,Ku70明显下调,其余蛋白的表达不受影响。稳定同位素标记定量蛋白组学方法鉴定出PARP1、ligase3和XRCC1在Ku70下调后在损伤染色质聚集增多。Western blot进行了验证并显示PARP1、ligase3和XRCC1在损伤染色质的聚集随DSB程度增加而增加。施加PARP1抑制剂DIQ,随着DIQ浓度的上升,ligase3在损伤染色质的聚集逐渐减少。 结论 沉默Ku70后,PARP1、ligase3和XRCC1在DSB染色质聚集增加,这种聚集与DSB程度变化一致
并且ligase3的染色质聚集具有一定程度的PARP1依赖性。
Objective To investigate the recruitment of base excision repair (BER) key factors
poly(ADP-ribose) polymerase 1 (PARP1)
ligase 3 and X-ray repair cross-complementing protein 1 (XRCC1) at chromatin with DNA double-strand break (DSB) after silencing Ku70
and the effect of PARP1 inhibition on the protein recruitment. Methods A cell line capable of inductively expressing Ku70 shRNA was treated with calicheamicin to induce DSB. Proteins recruited at the damaged chromatin after down-regulation of Ku70 expression were identified through stable isotope labeling by amino acids in cell culture (SILAC) and Western blotting
and the influence of PARP1 inhibitor
1
5-dihydroxyisoquinolin (DIQ)
on the protein recruitment was analyzed. Results Ku70 was down-regulated significantly by virtue of doxycycline
while the expression of other proteins was not influenced. The SILAC and Western blotting results showed that the recruitment of PARP1
ligase 3 and XRCC1 at the damaged chromatin increased after Ku70 down-regulation
and the recruitment of PARP1
ligase 3 and XRCC1 at the damaged chromatin increased with the increase of DSB degree. The recruitment of ligase 3 at the damaged chromatin decreased when the DIQ concentration increased. Conclusion Silencing Ku70 promotes the recruitment of PARP1
ligase 3 and XRCC1 at chromatin with DSB
and the protein recruitment is correlated positively to DSB degree. The recruitment of ligase 3 depends on PARP1 to some extent.
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