A novel lncRNA Discn fine-tunes replication protein A (RPA) availability to promote genomic stability

Lin Wang, Jingzheng Li, Hu Zhou, Weidao Zhang, Jing Gao and Ping Zheng ()
Additional contact information
Lin Wang: Kunming Institute of Zoology, Chinese Academy of Sciences
Jingzheng Li: Kunming Institute of Zoology, Chinese Academy of Sciences
Hu Zhou: Shanghai Institute of Materia Medica, Chinese Academy of Sciences
Weidao Zhang: Kunming Institute of Zoology, Chinese Academy of Sciences
Jing Gao: Shanghai Institute of Materia Medica, Chinese Academy of Sciences
Ping Zheng: Kunming Institute of Zoology, Chinese Academy of Sciences

Nature Communications, 2021, vol. 12, issue 1, 1-15

Abstract: Abstract RPA is a master regulator of DNA metabolism and RPA availability acts as a rate-limiting factor. While numerous studies focused on the post-translational regulations of RPA for its functions, little is known regarding how RPA availability is controlled. Here we identify a novel lncRNA Discn as the guardian of RPA availability in stem cells. Discn is induced upon genotoxic stress and binds to neucleolin (NCL) in the nucleolus. This prevents NCL from translocation into nucleoplasm and avoids undesirable NCL-mediated RPA sequestration. Thus, Discn-NCL-RPA pathway preserves a sufficient RPA pool for DNA replication stress response and repair. Discn loss causes massive genome instability in mouse embryonic stem cells and neural stem/progenigor cells. Mice depleted of Discn display newborn death and brain dysfunctions due to DNA damage accumulation and associated inflammatory reactions. Our findings uncover a key regulator of DNA metabolism and provide new clue to understand the chemoresistance in cancer treatment.

Date: 2021
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-021-25827-6 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25827-6

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-25827-6

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().