SUMO E3 ligase Mms21 prevents spontaneous DNA damage induced genome rearrangements.
Mms21, a subunit of the Smc5/6 complex, possesses an E3 ligase activity for the Small Ubiquitin-like MOdifier (SUMO). Here we show that the mms21-CH mutation, which inactivates Mms21 ligase activity, causes increased accumulation of gross chromosomal rearrangements (GCRs) selected in the dGCR assay....
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2018-03-01
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| Series: | PLoS Genetics |
| Online Access: | http://europepmc.org/articles/PMC5860785?pdf=render |
| _version_ | 1818988423597260800 |
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| author | Jason Liang Bin-Zhong Li Alexander P Tan Richard D Kolodner Christopher D Putnam Huilin Zhou |
| author_facet | Jason Liang Bin-Zhong Li Alexander P Tan Richard D Kolodner Christopher D Putnam Huilin Zhou |
| author_sort | Jason Liang |
| collection | DOAJ |
| description | Mms21, a subunit of the Smc5/6 complex, possesses an E3 ligase activity for the Small Ubiquitin-like MOdifier (SUMO). Here we show that the mms21-CH mutation, which inactivates Mms21 ligase activity, causes increased accumulation of gross chromosomal rearrangements (GCRs) selected in the dGCR assay. These dGCRs are formed by non-allelic homologous recombination between divergent DNA sequences mediated by Rad52-, Rrm3- and Pol32-dependent break-induced replication. Combining mms21-CH with sgs1Δ caused a synergistic increase in GCRs rates, indicating the distinct roles of Mms21 and Sgs1 in suppressing GCRs. The mms21-CH mutation also caused increased rates of accumulating uGCRs mediated by breakpoints in unique sequences as revealed by whole genome sequencing. Consistent with the accumulation of endogenous DNA lesions, mms21-CH mutants accumulate increased levels of spontaneous Rad52 and Ddc2 foci and had a hyper-activated DNA damage checkpoint. Together, these findings support that Mms21 prevents the accumulation of spontaneous DNA lesions that cause diverse GCRs. |
| first_indexed | 2024-12-20T19:22:21Z |
| format | Article |
| id | doaj.art-00067a1fbbd44eac8869d3e503a152c2 |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-12-20T19:22:21Z |
| publishDate | 2018-03-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-00067a1fbbd44eac8869d3e503a152c22022-12-21T19:28:57ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042018-03-01143e100725010.1371/journal.pgen.1007250SUMO E3 ligase Mms21 prevents spontaneous DNA damage induced genome rearrangements.Jason LiangBin-Zhong LiAlexander P TanRichard D KolodnerChristopher D PutnamHuilin ZhouMms21, a subunit of the Smc5/6 complex, possesses an E3 ligase activity for the Small Ubiquitin-like MOdifier (SUMO). Here we show that the mms21-CH mutation, which inactivates Mms21 ligase activity, causes increased accumulation of gross chromosomal rearrangements (GCRs) selected in the dGCR assay. These dGCRs are formed by non-allelic homologous recombination between divergent DNA sequences mediated by Rad52-, Rrm3- and Pol32-dependent break-induced replication. Combining mms21-CH with sgs1Δ caused a synergistic increase in GCRs rates, indicating the distinct roles of Mms21 and Sgs1 in suppressing GCRs. The mms21-CH mutation also caused increased rates of accumulating uGCRs mediated by breakpoints in unique sequences as revealed by whole genome sequencing. Consistent with the accumulation of endogenous DNA lesions, mms21-CH mutants accumulate increased levels of spontaneous Rad52 and Ddc2 foci and had a hyper-activated DNA damage checkpoint. Together, these findings support that Mms21 prevents the accumulation of spontaneous DNA lesions that cause diverse GCRs.http://europepmc.org/articles/PMC5860785?pdf=render |
| spellingShingle | Jason Liang Bin-Zhong Li Alexander P Tan Richard D Kolodner Christopher D Putnam Huilin Zhou SUMO E3 ligase Mms21 prevents spontaneous DNA damage induced genome rearrangements. PLoS Genetics |
| title | SUMO E3 ligase Mms21 prevents spontaneous DNA damage induced genome rearrangements. |
| title_full | SUMO E3 ligase Mms21 prevents spontaneous DNA damage induced genome rearrangements. |
| title_fullStr | SUMO E3 ligase Mms21 prevents spontaneous DNA damage induced genome rearrangements. |
| title_full_unstemmed | SUMO E3 ligase Mms21 prevents spontaneous DNA damage induced genome rearrangements. |
| title_short | SUMO E3 ligase Mms21 prevents spontaneous DNA damage induced genome rearrangements. |
| title_sort | sumo e3 ligase mms21 prevents spontaneous dna damage induced genome rearrangements |
| url | http://europepmc.org/articles/PMC5860785?pdf=render |
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