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S‐sulfhydration of MEK 1 leads to PARP ‐1 activation and DNA damage repair
Author(s) -
Zhao Kexin,
Ju YoungJun,
Li Shuangshuang,
Altaany Zaid,
Wang Rui,
Yang Guangdong
Publication year - 2014
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1002/embr.201338213
Subject(s) - chemistry , microbiology and biotechnology , biology
The repair of DNA damage is fundamental to normal cell development and replication. Hydrogen sulfide ( H 2 S ) is a novel gasotransmitter that has been reported to protect cellular aging. Here, we show that H 2 S attenuates DNA damage in human endothelial cells and fibroblasts by S ‐sulfhydrating MEK 1 at cysteine 341, which leads to PARP ‐1 activation. H 2 S‐induced MEK 1 S ‐sulfhydration facilitates the translocation of phosphorylated ERK 1/2 into nucleus, where it activates PARP ‐1 through direct interaction. Mutation of MEK 1 cysteine 341 inhibits ERK phosphorylation and PARP ‐1 activation. In the presence of H 2 S , activated PARP ‐1 recruits XRCC 1 and DNA ligase III to DNA breaks to mediate DNA damage repair, and cells are protected from senescence.