Journal
EMBO REPORTS
Volume 15, Issue 7, Pages 792-800Publisher
WILEY
DOI: 10.1002/embr.201338213
Keywords
H2S; MEK1; PARP-1; S-sulfhydration
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Funding
- Heart and Stroke Foundation of Canada
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The repair of DNA damage is fundamental to normal cell development and replication. Hydrogen sulfide (H2S) is a novel gasotransmitter that has been reported to protect cellular aging. Here, we show that H2S attenuates DNA damage in human endothelial cells and fibroblasts by S-sulfhydrating MEK1 at cysteine 341, which leads to PARP-1 activation. H2S-induced MEK1 S-sulfhydration facilitates the translocation of phosphorylated ERK1/2 into nucleus, where it activates PARP-1 through direct interaction. Mutation of MEK1 cysteine 341 inhibits ERK phosphorylation and PARP-1 activation. In the presence of H2S, activated PARP-1 recruits XRCC1 and DNA ligase III to DNA breaks to mediate DNA damage repair, and cells are protected from senescence.
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