7SK-snRNP 通过促进复制叉逆转与同源重组连接转录应激与复制应激的细胞响应
The 7SK small nuclear ribonucleoprotein links the cell responses to transcription and replication stress by promoting replication fork reversal and homologous recombination
7SK 小核核糖核蛋白（7SK-snRNP）通过促进 RAD51 介导的复制叉逆转和同源重组，把细胞对转录应激与复制应激的响应连接起来。研究发现，在同时造成复制与转录应激的试剂作用下，7SK-snRNP 促进复制叉减速，且这一作用不依赖其与转录–复制冲突的关系；在转录应激条件下，它还促进 RAD51 募集到复制相关双链断裂或复制后缺口，并支持直接双链断裂处的同源重组。相反，7SK-snRNP 组分并非羟基脲诱导的 RAD51 募集所必需。
来源：Nucleic Acids Research · doi.org
The 7SK small nuclear ribonucleoprotein (7SK-snRNP) releases positive transcription elongation factor b to sustain RNA polymerase II (RNAPII) activity during transcription stress. Many conditions that block transcription also cause replication stress, and 7SK-snRNP components have potential roles in transcription–replication conflicts and double-strand break (DSB) repair. Here, we investigate roles of 7SK-snRNP components in replication stress responses. We report that 7SK-snRNP promotes replication fork slowing in response to agents that cause both replication and transcription stress. Our data suggest that 7SK-snRNP facilitates RAD51-mediated replication fork reversal rather than transcription–replication conflicts. 7SK-snRNP also promotes RAD51 recruitment to replication-associated DSBs or post-replicative gaps under conditions of transcription stress and supports homologous recombination at direct DSBs. In contrast, 7SK-snRNP components are not required for RAD51 recruitment in response to hydroxyurea. Our data support that LARP7 functions during replication stress independently of its interaction with BRCA1, and that LARP7 and HEXIM1 promote survival of replication stress. 7SK-snRNP components are not recruited to stressed replication forks, and RNAPII inhibition phenocopies loss of these proteins. Our data support a model where 7SK-snRNP modulation of RNAPII activity helps facilitate several RAD51 functions under transcription stress conditions, thereby connecting the cell responses to transcription and replication stress.