Dataset Information

Acetylation-dependent function of human single-stranded DNA binding protein 1.

ABSTRACT: Human single-stranded DNA binding protein 1 (hSSB1) plays a critical role in responding to DNA damage and maintaining genome stability. However, the regulation of hSSB1 remains poorly studied. Here, we determined that hSSB1 acetylation at K94 mediated by the acetyltransferase p300 and the deacetylases SIRT4 and HDAC10 impaired its ubiquitin-mediated degradation by proteasomes. Moreover, we demonstrated that the hSSB1-K94R mutant had reduced cell survival in response to DNA damage by radiation or chemotherapy drugs. Furthermore, the p300/CBP inhibitor C646 significantly enhanced the sensitivity of cancer cells to chemotherapy drugs, and a positive correlation between hSSB1 and p300 level was observed in clinical colorectal cancer samples. Acetylation, a novel regulatory modification of hSSB1, is crucial for its function under both physiological and pathological conditions. This finding supports the notion that the combination of chemotherapy drugs with acetylation inhibitors may benefit cancer patients.

SUBMITTER: Wu Y

PROVIDER: S-EPMC4652753 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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Acetylation-dependent function of human single-stranded DNA binding protein 1.

Wu Yuanzhong Y Chen Hongxia H Lu Jinping J Zhang Meifang M Zhang Ruhua R Duan Tingmei T Wang Xin X Huang Jun J Kang Tiebang T

Nucleic acids research 20150713 16

Human single-stranded DNA binding protein 1 (hSSB1) plays a critical role in responding to DNA damage and maintaining genome stability. However, the regulation of hSSB1 remains poorly studied. Here, we determined that hSSB1 acetylation at K94 mediated by the acetyltransferase p300 and the deacetylases SIRT4 and HDAC10 impaired its ubiquitin-mediated degradation by proteasomes. Moreover, we demonstrated that the hSSB1-K94R mutant had reduced cell survival in response to DNA damage by radiation or ...[more]

PMID: 26170237

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Project description:Deinococcus radiodurans R1 is one of the most radiation-resistant organisms known and is able to repair an unusually large amount of DNA damage without induced mutation. Single-stranded DNA-binding (SSB) protein is an essential protein in all organisms and is involved in DNA replication, recombination and repair. The published genomic sequence from Deinococcus radiodurans includes a putative single-stranded DNA-binding protein gene (ssb; DR0100) requiring a translational frameshift for synthesis of a complete SSB protein. The apparently tripartite gene has inspired considerable speculation in the literature about potentially novel frameshifting or RNA editing mechanisms. Immediately upstream of the ssb gene is another gene (DR0099) given an ssb-like annotation, but left unexplored.A segment of the Deinococcus radiodurans strain R1 genome encompassing the ssb gene has been re-sequenced, and two errors involving omitted guanine nucleotides have been documented. The corrected sequence incorporates both of the open reading frames designated DR0099 and DR0100 into one contiguous ssb open reading frame (ORF). The corrected gene requires no translational frameshifts and contains two predicted oligonucleotide/oligosaccharide-binding (OB) folds. The protein has been purified and its sequence is closely related to the Thermus thermophilus and Thermus aquaticus SSB proteins. Like the Thermus SSB proteins, the SSBDr functions as a homodimer. The Deinococcus radiodurans SSB homodimer stimulates Deinococcus radiodurans RecA protein and Escherichia coli RecA protein-promoted DNA three-strand exchange reactions with at least the same efficiency as the Escherichia coli SSB homotetramer.The correct Deinococcus radiodurans ssb gene is a contiguous open reading frame that codes for the largest bacterial SSB monomer identified to date. The Deinococcus radiodurans SSB protein includes two OB folds per monomer and functions as a homodimer. The Deinococcus radiodurans SSB protein efficiently stimulates Deinococcus radiodurans RecA and also Escherichia coli RecA protein-promoted DNA strand exchange reactions. The identification and purification of Deinococcus radiodurans SSB protein not only allows for greater understanding of the SSB protein family but provides an essential yet previously missing player in the current efforts to understand the extraordinary DNA repair capacity of Deinococcus radiodurans.

Dataset Information

Acetylation-dependent function of human single-stranded DNA binding protein 1.

Publications

Acetylation-dependent function of human single-stranded DNA binding protein 1.

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