The RNF8 and RNF168 Ubiquitin Ligases Regulate Pro- and Anti-Resection Activities at Broken DNA Ends During Non-Homologous End Joining.

TitleThe RNF8 and RNF168 Ubiquitin Ligases Regulate Pro- and Anti-Resection Activities at Broken DNA Ends During Non-Homologous End Joining.
Publication TypeJournal Article
Year of Publication2021
AuthorsChen B-R, Wang Y, Shen Z-J, Bennett A, Hindi I, Tyler JK, Sleckman BP
JournalDNA Repair (Amst)
Volume108
Pagination103217
Date Published2021 Sep 01
ISSN1568-7856
Abstract

The RING-type E3 ubiquitin ligases RNF8 and RNF168 recruit DNA damage response (DDR) factors to chromatin flanking DNA double strand breaks (DSBs) including 53BP1, which protects DNA ends from resection during DNA DSB repair by non-homologous end joining (NHEJ). Deficiency of RNF8 or RNF168 does not lead to demonstrable NHEJ defects, but like deficiency of 53BP1, the combined deficiency of XLF and RNF8 or RNF168 leads to diminished NHEJ in lymphocytes arrested in G/G phase. The function of RNF8 in NHEJ depends on its E3 ubiquitin ligase activity. Loss of RNF8 or RNF168 in G/G-phase lymphocytes leads to the resection of broken DNA ends, demonstrating that RNF8 and RNF168 function to protect DNA ends from nucleases, pos sibly through the recruitment of 53BP1. However, the loss of 53BP1 leads to more severe resection than the loss of RNF8 or RNF168. Moreover, in 53BP1-deficient cells, the loss of RNF8 or RNF168 leads to diminished DNA end resection. We conclude that RNF8 and RNF168 regulate pathways that both prevent and promote DNA end resection in cells arrested in G/G phase.

DOI10.1016/j.dnarep.2021.103217
Alternate JournalDNA Repair (Amst)
PubMed ID34481157
Grant ListR01 CA095641 / CA / NCI NIH HHS / United States
R01 GM064475 / GM / NIGMS NIH HHS / United States
Related Faculty: 
Jessica K. Tyler, Ph.D.

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