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Abstract Cells rapidly respond to replication stress actively slowing fork progression and inducing fork reversal. How replication fork plasticity is achieved in the context of nuclear organization is currently unknown. Using nuclear actin probes in living and fixed cells, we visualized nuclear actin filaments in unperturbed S phase and observed their rapid extension in number and length upon genotoxic treatments, frequently taking contact with replication factories. Chemically or genetically impairing nuclear actin polymerization shortly before these treatments prevents active fork slowing and abolishes fork reversal. Defective fork remodeling is linked to deregulated chromatin loading of PrimPol, which promotes unrestrained and discontinuous DNA synthesis and limits the recruitment of RAD51 and SMARCAL1 to nascent DNA. Moreover, defective nuclear actin polymerization upon mild replication interference induces chromosomal instability in a PRIMPOL-dependent manner. Hence, by limiting PrimPol activity, nuclear F-actin orchestrates replication fork plasticity and is a key molecular determinant in the rapid cellular response to genotoxic treatments.
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The Local Forking Lemma and Its Application to Deterministic Encryption
We bypass impossibility results for the deterministic encryption of public-key-dependent messages, showing that, in this setting, the classical Encrypt-with-Hash scheme provides message-recovery security, across a broad range of message distributions. The proof relies on a new variant of the forking lemma in which the random oracle is reprogrammed on just a single fork point rather than on all points past the fork.
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- Award ID(s):
- 1717640
- PAR ID:
- 10200007
- Editor(s):
- Steven D. Galbraith, Shiho Moriai
- Date Published:
- Journal Name:
- Advances in Cryptology - {ASIACRYPT} 2019 - 25th International Conference on the Theory and Application of Cryptology and Information Security, Kobe, Japan, December 8-12, 2019, Proceedings, Part III
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Nuclear actin filaments (F-actin) form during S-phase and in response to replication stress to promote fork remodeling and repair. In mild replication stress conditions, nuclear actin polymerization is required to limit PrimPol recruitment to the fork while promoting fork reversal. Both short and long filaments form during this response, but their function in the nuclear dynamics of replication sites was unclear. Here, we show that replication centers associated with long nuclear actin filaments become more mobile than the rest of the forks, suggesting relocalization of replication sites as a response to prolonged fork stalling and/or fork breakage, even in response to mild replication stress.more » « less
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Conference Paper:
- https://doi.org/10.1007/978-3-030-34618-8_21
