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000601650 1001_ $$0P:(DE-H253)PIP1098105$$aCaragliano, Enrico$$b0
000601650 245__ $$aHuman cytomegalovirus forms phase-separated compartments at viral genomes to facilitate viral replication
000601650 260__ $$a[New York, NY]$$bElsevier$$c2022
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000601650 520__ $$aSummaryHuman cytomegalovirus (HCMV) replicates its DNA genome in specialized replication compartments (RCs) in the host cell nucleus. These membrane-less organelles originate as spherical structures and grow in size over time. However, the mechanism of RC biogenesis has remained understudied. Using live-cell imaging and photo-oligomerization, we show that a central component of RCs, the UL112-113 proteins, undergo liquid-liquid phase separation (LLPS) to form RCs in the nucleus. We show that the self-interacting domain and large intrinsically disordered regions of UL112-113 are required for LLPS. Importantly, viral DNA induces local clustering of these proteins and lowers the threshold for phase separation. The formation of phase-separated compartments around viral genomes is necessary to recruit the viral DNA polymerase for viral genome replication. Thus, HCMV uses its UL112-113 proteins to generate RCs around viral genomes by LLPS to ensure the formation of a pro-replicative environment. 
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000601650 7001_ $$0P:(DE-HGF)0$$aBonazza, Stefano$$b1
000601650 7001_ $$0P:(DE-HGF)0$$aFrascaroli, Giada$$b2
000601650 7001_ $$0P:(DE-HGF)0$$aTang, Jiajia$$b3
000601650 7001_ $$0P:(DE-H253)PIP1089262$$aSoh, Timothy K.$$b4
000601650 7001_ $$0P:(DE-H253)PIP1023782$$aGrünewald, Kay$$b5
000601650 7001_ $$0P:(DE-H253)PIP1082972$$aBosse, Jens Bernhard$$b6$$eCorresponding author
000601650 7001_ $$0P:(DE-HGF)0$$aBrune, Wolfram$$b7$$eCorresponding author
000601650 773__ $$0PERI:(DE-600)2649101-1$$a10.1016/j.celrep.2022.110469$$gVol. 38, no. 10, p. 110469 -$$n10$$p110469 $$tCell reports$$v38$$x2211-1247$$y2022
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