{"id":22599,"date":"2023-04-26T09:40:11","date_gmt":"2023-04-26T07:40:11","guid":{"rendered":"https:\/\/www.izb-online.de\/spezifische-verpackung-der-dna-beeinflusst-die-zellteilung-innovations-und-gruenderzentrum-biotechnologie-izb\/"},"modified":"2023-04-26T09:47:43","modified_gmt":"2023-04-26T07:47:43","slug":"specific-packaging-of-dna-affects-cell-division-innovations-und-gruenderzentrum-biotechnologie-izb","status":"publish","type":"post","link":"https:\/\/www.izb-online.de\/en\/izb-biotech-news\/specific-packaging-of-dna-affects-cell-division-innovations-und-gruenderzentrum-biotechnologie-izb\/","title":{"rendered":"Specific packaging of DNA affects cell division"},"content":{"rendered":"

[vc_row el_class=”gco-magazine-container”][vc_column el_class=”bildspalte”][vc_row_inner][vc_column_inner offset=”vc_col-lg-12 vc_col-md-12″][vc_column_text el_class=”gco-magazine–title”]<\/p>\n

Specific packaging of DNA affects cell division<\/h1>\n

[\/vc_column_text][vc_column_text el_class=”gco-magazine-lead”]LMU molecular biologists were able to show that, contrary to prevalent assumptions, this unique packaging is not just an obstacle, but a crucial element for replication.[\/vc_column_text][vc_column_text el_class=”gco-magazine–post-date”]April, 2023[\/vc_column_text][\/vc_column_inner][\/vc_row_inner][vc_row_inner el_class=”two-columns”][vc_column_inner el_class=”bild-zwei-spalten-links”][vc_single_image image=”22595″ img_size=”full”][vc_column_text el_class=”gco-magazine-copyright”]\u00a9 LMU[\/vc_column_text][vc_column_text el_class=”gco-magazine-picture-discription”]Dr. Christoph F. Kurat (laboratory director and last author of the study) at the Biomedical Center (BMC) of the LMU[\/vc_column_text][vc_single_image image=”22593″ img_size=”full”][vc_column_text el_class=”gco-magazine-copyright”]\u00a9 LMU[\/vc_column_text][vc_column_text el_class=”gco-magazine-picture-discription”]Erika Chacin (PhD student and first author of the study) and Dr. Christoph F. Kurat (laboratory manager and last author) at a \u04d2KTA pure™ chromatography system analyzing results of a protein purification.[\/vc_column_text][\/vc_column_inner][\/vc_row_inner][vc_row_inner el_class=”gco-magazine–quote” css=”.vc_custom_1611310713611{margin-top: 33px !important;}”][vc_column_inner][vc_column_text]<\/p>\n

\u201cIt is one of the very fundamental processes of life, and gaining a deeper understanding of it is important in its own right. In addition, both replication and the chromatin structure go awry in the case of cancer cells, for example. That we\u2019ve been able to bring these two aspects together could help with the development of better drugs in the future.\u201c<\/h6>\n

Dr. Christoph F. Kurat, Principal Investigator at LMU\u2019s Biomedical Center (BMC)<\/p>\n

[\/vc_column_text][\/vc_column_inner][\/vc_row_inner][vc_row_inner el_class=”gco-magazine-container–copy” css=”.vc_custom_1591795890737{margin-top: 21px !important;}”][vc_column_inner][vc_column_text]The DNA molecule is located in the cell nucleus as a densely packed complex of DNA and protein, known as chromatin. Wrapped in sections around a core of special proteins known as histones, the DNA forms so-called nucleosomes, which are organized along the DNA like pearls on a string. For one of the fundamental processes of life, replication, the doubling of DNA, the standard textbook view tended to see this literally tangled structure as a hindrance that had to be loosened up and overcome with the expenditure of energy. A team led by molecular biologist Dr. Christoph F. Kurat from LMU\u2019s Biomedical Center (BMC) has now shown that this is not the whole truth: At certain places in the genome, the starting points of replication, a characteristic nucleosome structure is crucial for replication to get going in the first place, as the researchers report in the journal Nature.<\/p>\n

Before a cell can divide, its DNA has to double. This process does not initiate at one place only, rather the molecular machines of replication get to work simultaneously at many starting points along the chromosomes. Human cells possess around 30,000 of these so-called replication origins, while the single-celled baker\u2019s yeast with a small genome, which Kurat\u2019s team investigated as a model organism, possesses around 400 of them. Some time ago, researchers had discovered characteristic chromatin structures at these origins: The nucleosomes at these sites are arranged in very regular fashion, \u201cin a much more orderly way than in the rest of the genome,\u201d says Kurat.<\/p>\n

Minimalist models in test tubes
\n<\/strong>To investigate how this structural regularity comes about and how it affects replication, Kurat and his team worked for years to isolate the proteins and origins involved in the replication of yeast cells, so that they could reproduce a functional replication system in test tubes. \u201cSuch a biochemical reconstitution approach is extremely laborious,\u201d emphasizes Kurat, \u201cbut also highly valuable for understanding complicated processes in detail. So it was a boon for us that we had such fruitful collaboration with colleagues at the BMC and at the Max Planck Institute for Biochemistry.\u201d<\/p>\n

With these reconstitutions, the researchers were able to demonstrate which factors generate the regular chromatin structure at the origins and how important this is for the replication machinery to get going at their starting points. \u201cMutated cells without this chromatin structure are not viable,\u201d says Erika Chacin, lead author of the study. A key factor for the start of replication is the protein complex ORC (Origin Recognition Complex), of which it has long been known that it recruits the necessary parts of the replication machines. To their surprise, the researchers discovered that this complex has a second function: It plays a crucial role in the genesis of the highly ordered chromatin structure at the origins, by arranging the nucleosomes accordingly in conjunction with so-called chromatin remodeler complexes.<\/p>\n

\u201cOur results give scientists a better understanding of replication,\u201d says Kurat. \u201cIt is one of the very fundamental processes of life, and gaining a deeper understanding of it is important in its own right. In addition, both replication and the chromatin structure go awry in the case of cancer cells, for example. That we\u2019ve been able to bring these two aspects together could help with the development of better drugs in the future. Many cancer drugs inhibit DNA replication, which is associated with strong side effects. The chromatin structure could be a new lever we could employ going forward.\u201d<\/p>\n

The paper is available here: www.nature.com\/articles\/s41586-023-05926-8<\/a>[\/vc_column_text][vc_column_text css=”.vc_custom_1583761043671{background-color: #1e73be !important;}” el_class=”redaktionell”][\/vc_column_text][\/vc_column_inner][\/vc_row_inner]\n\n

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