Cruciform structures are preferential targets for many architectural and regulatory proteins, as well as a number of DNA binding proteins with weak sequence specificity. Some of these proteins are also capable of inducing the formation of cruciform structures upon DNA binding. In this paper we analyzed the amino acid composition of eighteen cruciform binding proteins of Homo sapiens. Comparison with general amino acid frequencies in all human proteins revealed unique differences, with notable enrichment for lysine and serine and/or depletion for alanine, glycine, glutamine, arginine, tyrosine and tryptophan residues. Based on bootstrap resampling and fuzzy cluster analysis, multiple molecular mechanisms of interaction with cruciform DNA structures could be suggested, including those involved in DNA repair, transcription and chromatin regulation. The proteins DEK, HMGB1 and TOP1 in particular formed a very distinctive group. Nonetheless, a strong interaction network connecting nearly all the cruciform binding proteins studied was demonstrated. Data reported here will be very useful for future prediction of new cruciform binding proteins or even construction of predictive tool/web-based application.

• MeSH
• aminokyseliny chemie   MeSH
• chromatin MeSH
• chromozomální proteiny, nehistonové chemie   MeSH
• DNA vazebné proteiny chemie   MeSH
• DNA-topoisomerasy I chemie   MeSH
• konformace nukleové kyseliny MeSH
• lidé MeSH
• onkogenní proteiny chemie   MeSH
• protein HMGB1 chemie   MeSH
• proteiny vázající poly-ADP-ribosu chemie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Topoisomerase II (TOP2) relieves torsional stress by forming transient cleavage complex intermediates (TOP2ccs) that contain TOP2-linked DNA breaks (DSBs). While TOP2ccs are normally reversible, they can be "trapped" by chemotherapeutic drugs such as etoposide and subsequently converted into irreversible TOP2-linked DSBs. Here, we have quantified etoposide-induced trapping of TOP2ccs, their conversion into irreversible TOP2-linked DSBs, and their processing during DNA repair genome-wide, as a function of time. We find that while TOP2 chromatin localization and trapping is independent of transcription, it requires pre-existing binding of cohesin to DNA. In contrast, the conversion of trapped TOP2ccs to irreversible DSBs during DNA repair is accelerated 2-fold at transcribed loci relative to non-transcribed loci. This conversion is dependent on proteasomal degradation and TDP2 phosphodiesterase activity. Quantitative modeling shows that only two features of pre-existing chromatin structure-namely, cohesin binding and transcriptional activity-can be used to predict the kinetics of TOP2-induced DSBs.

• MeSH
• chromozomy genetika   MeSH
• DNA vazebné proteiny chemie   genetika   MeSH
• DNA-topoisomerasy typu II chemie   genetika   MeSH
• DNA chemie   genetika   MeSH
• dvouřetězcové zlomy DNA * MeSH
• etoposid chemie   MeSH
• genetická transkripce MeSH
• genová konverze genetika   MeSH
• HCT116 buňky MeSH
• inhibitory topoisomerasy II chemie   farmakologie   MeSH
• kinetika MeSH
• lidé MeSH
• multiproteinové komplexy chemie   genetika   MeSH
• oprava DNA genetika   MeSH
• proteiny vázající poly-ADP-ribosu chemie   genetika   MeSH
• torze mechanická MeSH
• translokace genetická genetika   MeSH
• zlomy chromozomů MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Intramural MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH