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Efficient Parvovirus Replication Requires CRL4-Targeted Depletion of p21 to Prevent Its Inhibitory Interaction with PCNA


Many DNA viruses induce and then exploit host cellular DNA damage responses to generate a suitable environment for their continued replication. Parvoviruses, important disease agents in both humans and animals, rely on host DNA polymerases to replicate their genomes in cell-cycle arrested cells. We show that efficient parvovirus replication requires the recruitment to viral replication compartments of a host cellular E3-ubiquitin ligase, CRL4Cdt2, to target the potent cell cycle regulator p21 for subsequent degradation. The DNA polymerase-δ cofactor PCNA provides a molecular platform for initial substrate recognition by this ligase, and subsequent p21 depletion prevents its continued interaction with PCNA which otherwise inhibits efficient viral replication. Virally-induced p21 degradation represents another way of promoting efficient replication of DNA polymerase-δ-dependent viruses.


Vyšlo v časopise: Efficient Parvovirus Replication Requires CRL4-Targeted Depletion of p21 to Prevent Its Inhibitory Interaction with PCNA. PLoS Pathog 10(4): e32767. doi:10.1371/journal.ppat.1004055
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004055

Souhrn

Many DNA viruses induce and then exploit host cellular DNA damage responses to generate a suitable environment for their continued replication. Parvoviruses, important disease agents in both humans and animals, rely on host DNA polymerases to replicate their genomes in cell-cycle arrested cells. We show that efficient parvovirus replication requires the recruitment to viral replication compartments of a host cellular E3-ubiquitin ligase, CRL4Cdt2, to target the potent cell cycle regulator p21 for subsequent degradation. The DNA polymerase-δ cofactor PCNA provides a molecular platform for initial substrate recognition by this ligase, and subsequent p21 depletion prevents its continued interaction with PCNA which otherwise inhibits efficient viral replication. Virally-induced p21 degradation represents another way of promoting efficient replication of DNA polymerase-δ-dependent viruses.


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Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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