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dc.contributor.authorHartlerode, Andrea J.
dc.contributor.authorGuan, Yinghua
dc.contributor.authorRajendran, Anbazhagan
dc.contributor.authorUra, Kiyoe
dc.contributor.authorSchotta, Gunnar
dc.contributor.authorXie, Anyong
dc.contributor.authorShah, Jagesh V.
dc.contributor.authorScully, Ralph
dc.date.accessioned2013-05-08T13:23:24Z
dc.date.issued2012
dc.identifier.citationHartlerode, Andrea J., Yinghua Guan, Anbazhagan Rajendran, Kiyoe Ura, Gunnar Schotta, Anyong Xie, Jagesh V. Shah, and Ralph Scully. 2012. Impact of histone H4 lysine 20 methylation on 53BP1 responses to chromosomal double strand breaks. PLoS ONE 7(11): e49211.en_US
dc.identifier.issn1932-6203en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:10611844
dc.description.abstractRecruitment of 53BP1 to chromatin flanking double strand breaks (DSBs) requires γH2AX/MDC1/RNF8-dependent ubiquitination of chromatin and interaction of 53BP1 with histone H4 methylated on lysine 20 (H4K20me). Several histone methyltransferases have been implicated in 53BP1 recruitment, but their quantitative contributions to the 53BP1 response are unclear. We have developed a multi-photon laser (MPL) system to target DSBs to subfemtoliter nuclear volumes and used this to mathematically model DSB response kinetics of MDC1 and of 53BP1. In contrast to MDC1, which revealed first order kinetics, the 53BP1 MPL-DSB response is best fitted by a Gompertz growth function. The 53BP1 MPL response shows the expected dependency on MDC1 and RNF8. We determined the impact of altered H4K20 methylation on 53BP1 MPL response kinetics in mouse embryonic fibroblasts (MEFs) lacking key H4K20 histone methyltransferases. This revealed no major requirement for the known H4K20 dimethylases Suv4-20h1 and Suv4-20h2 in 53BP1 recruitment or DSB repair function, but a key role for the H4K20 monomethylase, PR-SET7. The histone methyltransferase MMSET/WHSC1 has recently been implicated in 53BP1 DSB recruitment. We found that WHSC1 homozygous mutant MEFs reveal an alteration in balance of H4K20 methylation patterns; however, 53BP1 DSB responses in these cells appear normal.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi:10.1371/journal.pone.0049211en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3509127/pdf/en_US
dash.licenseLAA
dc.subjectBiologyen_US
dc.subjectBiochemistryen_US
dc.subjectNucleic Acidsen_US
dc.subjectDNAen_US
dc.subjectDNA modificationen_US
dc.subjectDNA repairen_US
dc.subjectBiophysicsen_US
dc.subjectGeneticsen_US
dc.subjectEpigeneticsen_US
dc.subjectHistone Modificationen_US
dc.subjectGene Expressionen_US
dc.subjectMolecular Cell Biologyen_US
dc.subjectChromosome Biologyen_US
dc.subjectChromatinen_US
dc.subjectPhysicsen_US
dc.subjectChromosome Structureen_US
dc.subjectChromosome Functionen_US
dc.titleImpact of Histone H4 Lysine 20 Methylation on 53BP1 Responses to Chromosomal Double Strand Breaksen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS ONEen_US
dash.depositing.authorGuan, Yinghua
dc.date.available2013-05-08T13:23:24Z
dc.identifier.doi10.1371/journal.pone.0049211*
dash.contributor.affiliatedXie, Anyong
dash.contributor.affiliatedGuan, Yinghua
dash.contributor.affiliatedShah, Jagesh
dash.contributor.affiliatedScully, Ralph
dash.contributor.affiliatedRajendran, Anbazhagan


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