Journal
JOURNAL OF CELL BIOLOGY
Volume 149, Issue 4, Pages 799-809Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.149.4.799
Keywords
replication protein A; nucleolin; nucleolus; SV-40; heat shock
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Funding
- NCI NIH HHS [P30CA16087] Funding Source: Medline
- NIAID NIH HHS [AI29963] Funding Source: Medline
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We used a biochemical screen to identify nucleolin, a key factor in ribosome biogenesis, as a high-affinity binding partner for the heterotrimeric human replication protein A (hRPA). Binding studies in vitro demonstrated that the two proteins physically interact: with nucleolin using an unusual contact with the small hRPA subunit. Nucleolin significantly inhibited both simian virus 40 (SV-40) origin unwinding and SV-40 DNA replication in vitro, likely by nucleolin preventing hRPA from productive interaction with the SV-40 initiation complex. In vivo, use of epifluorescence and confocal microscopy showed that heat shock caused a dramatic redistribution of nucleolin from the nucleolus to the nucleoplasm. Nucleolin relocalization was concomitant with a tenfold increase in nucleolin-hRPA complex formation. The relocalized nucleolin significantly overlapped with the position of hRPA, but only poorly with sites of ongoing DNA synthesis. We suggest that the induced nucleolin-hRPA interaction signifies a novel mechanism that represses chromosomal replication after cell stress.
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