Ubc9- and mms21-mediated sumoylation counteracts recombinogenic events at damaged replication forks
- PMID: 17081974
- DOI: 10.1016/j.cell.2006.08.050
Ubc9- and mms21-mediated sumoylation counteracts recombinogenic events at damaged replication forks
Abstract
The Ubc9 SUMO-conjugating enzyme and the Siz1 SUMO ligase sumoylate several repair and recombination proteins, including PCNA. Sumoylated PCNA binds Srs2, a helicase counteracting certain recombination events. Here we show that ubc9 mutants depend on checkpoint, recombination, and replication genes for growth. ubc9 cells maintain stalled-fork stability but exhibit a Rad51-dependent accumulation of cruciform structures during replication of damaged templates. Mutations in the Mms21 SUMO ligase resemble the ubc9 mutations. However, siz1, srs2, or pcna mutants altered in sumoylation do not exhibit the ubc9/mms21 phenotype. Like ubc9/mms21 mutants, sgs1 and top3 mutants also accumulate X molecules at damaged forks, and Sgs1/BLM is sumoylated. We propose that Ubc9 and Mms21 act in concert with Sgs1 to resolve the X structures formed during replication. Our results indicate that Ubc9- and Mms21-mediated sumoylation functions as a regulatory mechanism, different from that of replication checkpoints, to prevent pathological accumulation of cruciform structures at damaged forks.
Comment in
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A SUMOry of DNA replication: synthesis, damage, and repair.Cell. 2006 Nov 3;127(3):455-7. doi: 10.1016/j.cell.2006.10.019. Cell. 2006. PMID: 17081966
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