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Biotinylation of histones: Physiological importance

Nagarama Kothapalli, University of Nebraska - Lincoln

Abstract

Posttranslational modifications of histones play essential roles in remodeling of chromatin structure and DNA repair. Biotinylation of histones is a recently identified modification. Here, we investigated the biological roles of biotinylation of lysine(K)-12 in histone H4 and the cellular distribution of biotinylating enzyme, holocarboxylase synthetase (HCS). ^ Biotinylation of K12 in histone H4 is an early signaling event in response to double strand breaks. K12 biotinylation in histone H4 decreased rapidly and transiently in human choriocarcinoma (JAr) cells after 20 min of DNA damage and returned to basal levels by 120 min. Biotinylated-K12 histone H4 decreased earlier than S14-phosphorylated histone H2B and poly(ADP-ribosylated) histone H2A known markers of DNA double strand breaks. Decrease in biotinylation of K12 in histone H4 was specific for double strand break and not tissue specific. Biotin deficiency led to decreased cell survival rates in response to DNA double strand breaks. ^ In another study, NCI-H69 small cell lung cancer cells, arrested in various phases of the cell cycle, showed distinct patterns of histone biotinylation. Biotinylation of K12 in histone H4 increased during G2 and M phase, and decreased during S phase. Biotinylation of K8 in histone H4 decreased in G1 phase and was maximal during G2 and M phase. This suggests that biotinylation of histones might play a role in cell proliferation and mitotic chromatin condensation. ^ Finally, we tested the correlation of HCS and p53, known to function both in DNA damage signaling and cell cycle. We tested this correlation using HCT 116 human colon cancer cells deficient in p53 and wild-type controls. The abundance of K12-biotinylated histone H4 and biotinylated carboxylases was decreased in p53 -/- HCT 116 cells compared to controls. Decreased carboxylase activities were observed in two distinct p53 -/- cells. An impaired nuclear translocation of HCS was observed in p53 -/- cells. Effects of p53 on decreased abundance of biotinylated histones were independent of HCS expression, histone debiotinylase activities, or biotin transport suggesting that the effects observed were due to impaired nuclear localization of HCS. ^

Subject Area

Chemistry, Biochemistry

Recommended Citation

Kothapalli, Nagarama, "Biotinylation of histones: Physiological importance" (2006). ETD collection for University of Nebraska - Lincoln. AAI3199698.
http://digitalcommons.unl.edu/dissertations/AAI3199698

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