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Crosstalk between CST and RPA regulates RAD51 activity during replication stress.
- Source :
-
Nature communications [Nat Commun] 2021 Nov 05; Vol. 12 (1), pp. 6412. Date of Electronic Publication: 2021 Nov 05. - Publication Year :
- 2021
-
Abstract
- Replication stress causes replication fork stalling, resulting in an accumulation of single-stranded DNA (ssDNA). Replication protein A (RPA) and CTC1-STN1-TEN1 (CST) complex bind ssDNA and are found at stalled forks, where they regulate RAD51 recruitment and foci formation in vivo. Here, we investigate crosstalk between RPA, CST, and RAD51. We show that CST and RPA localize in close proximity in cells. Although CST stably binds to ssDNA with a high affinity at low ionic strength, the interaction becomes more dynamic and enables facilitated dissociation at high ionic strength. CST can coexist with RPA on the same ssDNA and target RAD51 to RPA-coated ssDNA. Notably, whereas RPA-coated ssDNA inhibits RAD51 activity, RAD51 can assemble a functional filament and exhibit strand-exchange activity on CST-coated ssDNA at high ionic strength. Our findings provide mechanistic insights into how CST targets and tethers RAD51 to RPA-coated ssDNA in response to replication stress.<br /> (© 2021. The Author(s).)
- Subjects :
- DNA Replication genetics
DNA Replication physiology
Electrophoretic Mobility Shift Assay
HEK293 Cells
HeLa Cells
Humans
Immunoprecipitation
Protein Binding
Rad51 Recombinase genetics
Replication Protein A genetics
Saccharomyces cerevisiae genetics
Saccharomyces cerevisiae metabolism
Saccharomyces cerevisiae Proteins genetics
Saccharomyces cerevisiae Proteins metabolism
Rad51 Recombinase metabolism
Replication Protein A metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 12
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 34741010
- Full Text :
- https://doi.org/10.1038/s41467-021-26624-x