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S-sulfhydration of MEK1 leads to PARP-1 activation and DNA damage repair.

ABSTRACT: 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.

SUBMITTER: Zhao K

PROVIDER: S-EPMC4196983 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

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S-sulfhydration of MEK1 leads to PARP-1 activation and DNA damage repair.

Zhao Kexin K Ju YoungJun Y Li Shuangshuang S Altaany Zaid Z Wang Rui R Yang Guangdong G

EMBO reports 20140428 7

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 interactio ...[more]

PMID: 24778456

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