Tyrosine phosphorylation enhances RAD52-mediated annealing by modulating its DNA binding.
Tyrosine phosphorylation enhances RAD52-mediated annealing by modulating its DNA binding.
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酪氨酸磷酸化通过调节其DNA结合来增强RAD52介导的退火。
DOI：
10.1038/emboj.2011.238
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发表时间：
2011-07-29
期刊：
影响因子：
11.4
通讯作者：
Spies, Maria
中科院分区：
文献类型：
--
作者：
Honda, Masayoshi;Okuno, Yusuke;Yoo, Jungmin;Ha, Taekjip;Spies, Maria
RAD52 protein has an important role in homology-directed DNA repair by mediating RAD51 nucleoprotein filament formation on single-stranded DNA (ssDNA) protected by replication protein-A (RPA) and annealing of RPA-coated ssDNA. In human, cellular response to DNA damage includes phosphorylation of RAD52 by c-ABL kinase at tyrosine 104. To address how this phosphorylation modulates RAD52 function, we used an amber suppressor technology to substitute tyrosine 104 with chemically stable phosphotyrosine analogue (p-Carboxymethyl-L-phenylalanine, pCMF). The RAD52Y104pCMF retained ssDNA-binding activity characteristic of unmodified RAD52 but showed lower affinity for double-stranded DNA (dsDNA) binding. Single-molecule analyses revealed that RAD52Y104pCMF specifically targets and wraps ssDNA. While RAD52Y104pCMF is confined to ssDNA region, unmodified RAD52 readily diffuses into dsDNA region. The Y104pCMF substitution also increased the ssDNA annealing rate and allowed overcoming the inhibitory effect of dsDNA. We propose that phosphorylation at Y104 enhances ssDNA annealing activity of RAD52 by attenuating dsDNA binding. Implications of phosphorylation-mediated activation of RAD52 annealing activity are discussed.
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