Replisome loading reduces chromatin motion independent of DNA synthesis

dc.contributor.author Pabba, Maruthi Kumar
dc.contributor.author Ritter, Christian
dc.contributor.author Chagin, Vadim
dc.contributor.author Stear, Jeffrey
dc.contributor.author Loerke, Dinah
dc.contributor.author Prorok, Paulina
dc.contributor.author Schmid, Alice Kristin
dc.contributor.author Leonhardt, Heinrich
dc.contributor.author Rohr, Karl
dc.contributor.author Cardoso, Cristina
dc.contributor.author Kolobynina, Ksenia
dc.contributor.author Celikay, Kerem
dc.contributor.author Kolobynina, Ksenia
dc.date.accessioned 2023-07-07T11:56:08Z
dc.date.available 2022-05-11T07:21:00Z
dc.date.available 2023-07-07T11:56:08Z
dc.date.created 2022
dc.date.issued 2023-07-07
dc.description Chromatin has been shown to undergo diffusional motion, and during active gene transcription the RNA polymerase activity negatively affects chromatin motion. However, the relationship between chromatin motion and other genomic processes remains unclear. Hence, we set out to label the DNA directly in a sequence unbiased manner and recorded labeled chromatin dynamics in interphase human cells expressing GFP-tagged PCNA, a cell cycle marker and core component of the replication machinery. We detected decreased chromatin mobility during S-phase compared to G1 and G2 phases using automated particle tracking. To gain insight into the organization and dynamics of the genome during DNA replication, we analyzed labeled chromatin domain size and motion in replicating cells. By correlating chromatin mobility with proximity to sites of active DNA synthesis, we show that chromatin motion is locally constrained at the sites of DNA replication. Furthermore, inhibiting DNA synthesis activity leads to increase loading of DNA polymerases and further restricts local chromatin motion. The polymerases under stress no longer reel DNA through, as they normally do during DNA synthesis, which may explain the further restriction of chromatin motion and the fact that loading the helicase/polymerase already restricts it during active DNA synthesis. We, therefore, propose that increased polymerase loading but not their catalytic activity reduces genome dynamics and its accessibility and interaction with other genomic regions. de_DE
dc.description.version Prepublication with Access for Reviewer de_DE
dc.identifier.uri https://tudatalib.ulb.tu-darmstadt.de/handle/tudatalib/3462.2
dc.language.iso en de_DE
dc.rights.licenseCC-BY-NC-4.0 (https://creativecommons.org/licenses/by-nc/4.0)
dc.subject Aphidicolin de_DE
dc.subject cell cycle de_DE
dc.subject chromatin tracking de_DE
dc.subject diffusion de_DE
dc.subject DNA labeling de_DE
dc.subject DNA replication de_DE
dc.subject genome architecture de_DE
dc.subject hydroxyurea de_DE
dc.subject mean square displacement de_DE
dc.subject S-phase de_DE
dc.subject.classification 2.11-03
dc.subject.ddc 570
dc.title Replisome loading reduces chromatin motion independent of DNA synthesis de_DE
dc.type Software de_DE
dc.type Image de_DE
dcterms.accessRights openAccess
person.identifier.orcid #PLACEHOLDER_PARENT_METADATA_VALUE#
person.identifier.orcid #PLACEHOLDER_PARENT_METADATA_VALUE#
person.identifier.orcid #PLACEHOLDER_PARENT_METADATA_VALUE#
person.identifier.orcid 0000-0002-2255-8297
person.identifier.orcid 0000-0002-2068-0408
person.identifier.orcid #PLACEHOLDER_PARENT_METADATA_VALUE#
person.identifier.orcid #PLACEHOLDER_PARENT_METADATA_VALUE#
person.identifier.orcid #PLACEHOLDER_PARENT_METADATA_VALUE#
person.identifier.orcid #PLACEHOLDER_PARENT_METADATA_VALUE#
person.identifier.orcid #PLACEHOLDER_PARENT_METADATA_VALUE#
person.identifier.orcid 0000-0002-8035-8867
person.identifier.orcid #PLACEHOLDER_PARENT_METADATA_VALUE#
person.identifier.orcid 0000-0002-8035-8867
tuda.history.classification Version=2020-2024;201-03 Zellbiologie
tuda.project DFG | SFB1361,TP06 | TP_06_Cardoso_Mainz
tuda.project DFG | CA198/9-2 | Hochauflösende Analy
tuda.project DFG | CA198/15-1 | Regulation der Säuge
tuda.unit TUDa

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