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Volume 32, No 3, Mar 2022
ISSN: 1001-0602
EISSN: 1748-7838 2018
impact factor 17.848*
(Clarivate Analytics, 2019)
Volume 32 Issue 3, March 2022: 254-268
Pre-ribosomal RNA reorganizes DNA damage repair factors in nucleus during meiotic prophase and DNA damage response
Xiaochen Gai1,2,3,† , Di Xin1,2,3,† , Duo Wu1,2,3,† , Xin Wang1,2,3,† , Linlin Chen1,2,3 , Yiqing Wang1,2,3 , Kai Ma1,2,3 , Qilin Li1,2,3 , Peng Li1,2,3 , Xiaochun Yu1,2,3,*
1Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, ChinaIn response to DNA double-strand breaks (DSBs), DNA damage repair factors are recruited to DNA lesions and form nuclear foci. However, the underlying molecular mechanism remains largely elusive. Here, by analyzing the localization of DSB repair factors in the XY body and DSB foci, we demonstrate that pre-ribosomal RNA (pre-rRNA) mediates the recruitment of DSB repair factors around DNA lesions. Pre-rRNA exists in the XY body, a DSB repair hub, during meiotic prophase, and colocalizes with DSB repair factors, such as MDC1, BRCA1 and TopBP1. Moreover, pre-rRNA-associated proteins and RNAs, such as ribosomal protein subunits, RNase MRP and snoRNAs, also localize in the XY body. Similar to those in the XY body, pre-rRNA and ribosomal proteins also localize at DSB foci and associate with DSB repair factors. RNA polymerase I inhibitor treatment that transiently suppresses transcription of rDNA but does not affect global protein translation abolishes foci formation of DSB repair factors as well as DSB repair. The FHA domain and PST repeats of MDC1 recognize pre-rRNA and mediate phase separation of DSB repair factors, which may be the molecular basis for the foci formation of DSB repair factors during DSB response.
https://doi.org/10.1038/s41422-021-00597-4
