The post-translational modification of DNA damage response proteins with SUMO is an important mechanism to orchestrate a timely and orderly recruitment of repair factors to damage sites. After DNA replication stress and double-strand break formation, a number of repair factors are SUMOylated and interact with other SUMOylated factors, including the Yen1 nuclease. Yen1 plays a critical role in ensuring genome stability and unperturbed chromosome segregation by removing covalently linked DNA intermediates between sister chromatids that are formed by homologous recombination. Here we show how this important role of Yen1 depends on interactions mediated by non-covalent binding to SUMOylated partners. Mutations in the motifs that allow SUMO-mediated recruitment of Yen1 impair its ability to resolve DNA intermediates and result in chromosome mis-segregation and increased genome instability.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8986097 | PMC |
http://dx.doi.org/10.1371/journal.pgen.1009860 | DOI Listing |
Nat Commun
December 2024
State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, The Chinese Academy of Agricultural Sciences, Harbin, China.
Human ANP32A/B (huANP32A/B) poorly support the polymerase activity of avian influenza viruses (AIVs), thereby limiting interspecies transmission of AIVs from birds to humans. The SUMO-interacting motif (SIM) within NS2 promotes the adaptation of AIV polymerase to huANP32A/B via a yet undisclosed mechanism. Here we show that huANP32A/B are SUMOylated by the E3 SUMO ligase PIAS2α, and deSUMOylated by SENP1.
View Article and Find Full Text PDFNat Commun
October 2024
Department of Medicine, Division of Hematology and Medical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
SUMOylation regulates numerous cellular stress responses, yet targets in the apoptotic machinery remain elusive. We show that a single, DNA damage-induced monoSUMOylation event controls PIDDosome (PIDD1/RAIDD/caspase-2) formation and apoptotic death in response to unresolved DNA interstrand crosslinks (ICLs). SUMO-1 conjugation occurs on conserved K879 in the PIDD1 death domain (DD); is catalyzed by PIAS1 and countered by SENP3; and is triggered by ATR phosphorylation of neighboring T788 in the PIDD1 DD, which enables PIAS1 docking.
View Article and Find Full Text PDFPLoS Genet
March 2022
Université Paris-Saclay-UMR9019 CNRS-Gustave Roussy, Villejuif, France.
Nucleic Acids Res
March 2016
Institute of Molecular Biology, Academia Sinica, Taipei 115, Taiwan
Double-strand breaks (DSBs) in chromosomes are the most challenging type of DNA damage. The yeast and mammalian Mre11-Rad50-Xrs2/Nbs1 (MRX/N)-Sae2/Ctp1 complex catalyzes the resection of DSBs induced by secondary structures, chemical adducts or covalently-attached proteins. MRX/N also initiates two parallel DNA damage responses-checkpoint phosphorylation and global SUMOylation-to boost a cell's ability to repair DSBs.
View Article and Find Full Text PDFJ Biol Chem
December 2014
From the Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556
The 5 S rRNA gene-specific transcription factor IIIA (TFIIIA) interacts with the small ubiquitin-like modifier (SUMO) E3 ligase PIAS2b and with one of its targets, the transcriptional corepressor, XCtBP. PIAS2b is restricted to the cytoplasm of Xenopus oocytes but relocates to the nucleus immediately after fertilization. Following the midblastula transition, PIAS2b and XCtBP are present on oocyte-type, but not somatic-type, 5 S rRNA genes up through the neurula stage, as is a limiting amount of TFIIIA.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!