Wss1 Promotes Replication Stress Tolerance by Degrading Histones

Maddi, Karthik; Sam, Daniel Kwesi; Bonn, Florian; Prgomet, Stefan; Tulowetzke, Eric; Akutsu, Masato; López-Mosqueda, Jaime; Đikić, Ivan

doi:10.1016/j.celrep.2020.02.018

Cited by 16 publications

(13 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Validation of this hypothetical order of steps in proteolysis of DHC by the proteasome and Spartan requires more research. However, a recent study proved that Wss1 is actively involved in histone proteolysis in a NCP during replication stress (Maddi et al, 2020). Although this study showed that Wss1 removes histones non-covalently bound to DNA, it is very likely that this protease can also remove histones covalently cross-linked to DNA.…”

Section: Metalloprotease-based Proteolysis Of Histones Cross-linked Tmentioning

confidence: 77%

DNA-Histone Cross-Links: Formation and Repair

Pachva¹,

Kisselev

Matkarimov

et al. 2020

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

The nucleosome is a stretch of DNA wrapped around a histone octamer. Electrostatic interactions and hydrogen bonds between histones and DNA are vital for the stable organization of nucleosome core particles, and for the folding of chromatin into more compact structures, which regulate gene expression via controlled access to DNA. As a drawback of tight association, under genotoxic stress, DNA can accidentally cross-link to histone in a covalent manner, generating a highly toxic DNA-histone cross-link (DHC). DHC is a bulky lesion that can impede DNA transcription, replication, and repair, often with lethal consequences. The chemotherapeutic agent cisplatin, as well as ionizing and ultraviolet irradiations and endogenously occurring reactive aldehydes, generate DHCs by forming either stable or transient covalent bonds between DNA and side-chain amino groups of histone lysine residues. The mechanisms of DHC repair start to unravel, and certain common principles of DNA-protein cross-link (DPC) repair mechanisms that participate in the removal of cross-linked histones from DNA have been described. In general, DPC is removed via a two-step repair mechanism. First, cross-linked proteins are degraded by specific DPC proteases or by the proteasome, relieving steric hindrance. Second, the remaining DNA-peptide cross-links are eliminated in various DNA repair pathways. Delineating the molecular mechanisms of DHC repair would help target specific DNA repair proteins for therapeutic intervention to combat tumor resistance to chemotherapy and radiotherapy.

show abstract

Section: Metalloprotease-based Proteolysis Of Histones Cross-linked Tmentioning

confidence: 77%

DNA-Histone Cross-Links: Formation and Repair

Pachva¹,

Kisselev

Matkarimov

et al. 2020

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

show abstract

“…Even through non-covalent interaction, certain proteins such as yeast Fob1 or E. coli Tus can form effective DPC-like stable, high-affinity complexes with DNA that block replication fork movement [ 55 ]. Recently, histones in such non-covalent DPCs were shown to be substrates for Wss1 [ 56 ]. We postulate that Top1 mutants Y727F and Y740STOP, if forming replication barriers through high-affinity interaction with G4 DNA, could be SUMOylated and targeted by Wss1-dependent proteolysis.…”

Section: Discussionmentioning

confidence: 99%

Cleavage-defective Topoisomerase I mutants sharply increase G-quadruplex-associated genomic instability

Berroyer¹,

Bacolla²,

Tainer³

et al. 2022

Microb Cell

View full text Add to dashboard Cite

Topoisomerase 1 (Top1) removes transcription-associated helical stress to suppress G4-formation and its induced recombination at genomic loci containing guanine-run containing sequences. Interestingly, Top1 binds tightly to G4 structures, and its inhibition or depletion can cause elevated instability at these genomic loci. Top1 is targeted by the widely used anti-cancer chemotherapeutic camptothecin (CPT) and its derivatives, which stabilize Top1 covalently attached on a DNA nick and prevent the re-ligation step. Here we investigated how CPT-resistance conferring Top1 mutants, which emerge in cancer patients and cells treated with CPT, affect G4-induced genomic instability in S. cerevisiae. We found that Top1 mutants form stable complexes with G4 DNA and that expression of Top1 cleavage-defective mutants but not a DNA-binding-defective mutant lead to significantly elevated instability at a G4-forming genomic locus. Elevated recombination rates were partly suppressed by their proteolytic removal by SPRTN homolog Wss1 SUMO-dependent metalloprotease in vivo. Furthermore, interaction between G4-DNA binding protein Nsr1, a homolog to clinically-relevant human nucleolin, and Top1 mutants lead to a synergistic increase in G4-associated recombination. These results in the yeast system are strengthened by our cancer genome data analyses showing that functionally detrimental mutations in Top1 correlate with an enrichment of mutations at G4 motifs. Our collective experimental and computational findings point to cooperative binding of Top1 cleavage-defective mutants and Nsr1 as promoting DNA replication blockage and exacerbating genomic instability at G4-motifs, thus complicating patient treatment.

show abstract

“…This would explain the massive increase of unrepaired DSBs in the corresponding teb wss1A double mutant. Thus, in WT plants, WSS1A is able to suppress aberrant DSB formation by directly removing the replication-stalling obstacle or by protecting the stalled replication forks (Stingele et al, 2014;Enderle et al, 2019a;Maddi et al, 2020). We assume that the DSB-preventing function during replication is a conserved feature of WSS1A homologs in general.…”

Section: Wss1a Suppresses Formation Of Persisting Dsbmentioning

confidence: 93%

“…For WSS1A and RTR homologs, essential functions in maintaining replication fork stability were demonstrated in yeast and mammals. ScWss1 is able to degrade histones, which assemble at long single-stranded DNA straps of stalled replication forks, and thus the replication fork can be restored (Maddi et al, 2020). In humans, both RMI1 and the RECQ4A homolog BLM have been shown to interact with longer single-stranded DNA stretches coated by RPA.…”

Section: Wss1a Is Required For Replicative Dna Repairmentioning

confidence: 99%

The DNA‐dependent protease AtWSS1A suppresses persistent double strand break formation during replication

et al. 2021

View full text Add to dashboard Cite

The protease WSS1A is an important factor in the repair of DNA-protein crosslinks in plants.Here we show that the loss of WSS1A leads to a reduction of 45S rDNA repeats and chromosomal fragmentation in Arabidopsis. Moreover, in the absence of any factor of the RTR (RECQ4A/TOP3a/RMI1/2) complex, which is involved in the dissolution of DNA replication intermediates, WSS1A becomes essential for viability.If WSS1A loss is combined with loss of the classical (c) or alternative (a) nonhomologous end joining (NHEJ) pathways of double-strand break (DSB) repair, the resulting mutants show proliferation defects and enhanced chromosome fragmentation, which is especially aggravated in the absence of aNHEJ. This indicates that WSS1A is involved either in the suppression of DSB formation or in DSB repair itself. To test the latter we induced DSB by CRISPR/Cas9 at different loci in wild-type and mutant cells and analyzed their repair by deep sequencing. However, no change in the quality of the repair events and only a slight increase in their quantity was found.Thus, by removing complex DNA-protein structures, WSS1A seems to be required for the repair of replication intermediates which would otherwise be resolved into persistent DSB leading to genome instability.

show abstract

Wss1 Promotes Replication Stress Tolerance by Degrading Histones

Abstract: Highlights d Wss1 promotes replication stress tolerance d Wss1 catalytic activity is essential for replication stress tolerance d Histone accumulation is toxic to Wss1 mutant cells during replication stress d Wss1 targets histones bound to single-stranded DNA during replication stress

Cited by 16 publications

References 37 publications

DNA-Histone Cross-Links: Formation and Repair

DNA-Histone Cross-Links: Formation and Repair

Cleavage-defective Topoisomerase I mutants sharply increase G-quadruplex-associated genomic instability

The DNA‐dependent protease AtWSS1A suppresses persistent double strand break formation during replication

Contact Info

Product

Resources

About