期刊
ELIFE
卷 10, 期 -, 页码 -出版社
eLIFE SCIENCES PUBL LTD
DOI: 10.7554/eLife.70535
关键词
DNA replication; liquid phase condensates; intrinsically disordered proteins; DNA binding proteins; D; melanogaster
类别
资金
- NIH NRSA postdoctoral fellowship [F32GM116393]
- UC Berkeley Jesse Rabinowitz Award
- NCI [R01CA030490]
- NIGMS [R01GM141045-01]
- CPRIT [RR200070]
- Welch foundation [I-2074-20210327]
Researchers demonstrate that phase separation is driven by a synergy between electrostatic DNA-bridging interactions and hydrophobic inter-IDR contacts, dependent on sequence composition but not order. These interactions are resistant to 1,6-hexanediol and independent of aromaticity, revealing distinct mechanisms underlying condensate formation and specificity in different phase-separating systems.
Liquid-liquid phase separation (LLPS) of intrinsically disordered regions (IDRs) in proteins can drive the formation of membraneless compartments in cells. Phase-separated structures enrich for specific partner proteins and exclude others. Previously, we showed that the IDRs of metazoan DNA replication initiators drive DNA-dependent phase separation in vitro and chromosome binding in vivo, and that initiator condensates selectively recruit replication-specific partner proteins (Parker et al., 2019). How initiator IDRs facilitate LLPS and maintain compositional specificity is unknown. Here, using Drosophila melanogaster (Dm) Cdt1 as a model initiation factor, we show that phase separation results from a synergy between electrostatic DNA-bridging interactions and hydrophobic inter-IDR contacts. Both sets of interactions depend on sequence composition (but not sequence order), are resistant to 1,6-hexanediol, and do not depend on aromaticity. These findings demonstrate that distinct sets of interactions drive condensate formation and specificity across different phase-separating systems and advance efforts to predict IDR LLPS propensity and partner selection a priori.
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