Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Your Environment. Your Health.

Publication Detail

Title: Translesion polymerase kappa-dependent DNA synthesis underlies replication fork recovery.

Authors: Tonzi, Peter; Yin, Yandong; Lee, Chelsea Wei Ting; Rothenberg, Eli; Huang, Tony T

Published In Elife, (2018 11 13)

Abstract: DNA replication stress is often defined by the slowing or stalling of replication fork progression leading to local or global DNA synthesis inhibition. Failure to resolve replication stress in a timely manner contribute toward cell cycle defects, genome instability and human disease; however, the mechanism for fork recovery remains poorly defined. Here, we show that the translesion DNA polymerase (Pol) kappa, a DinB orthologue, has a unique role in both protecting and restarting stalled replication forks under conditions of nucleotide deprivation. Importantly, Pol kappa-mediated DNA synthesis during hydroxyurea (HU)-dependent fork restart is regulated by both the Fanconi Anemia (FA) pathway and PCNA polyubiquitination. Loss of Pol kappa prevents timely rescue of stalled replication forks, leading to replication-associated genomic instability, and a p53-dependent cell cycle defect. Taken together, our results identify a previously unanticipated role for Pol kappa in promoting DNA synthesis and replication stress recovery at sites of stalled forks.

PubMed ID: 30422114 Exiting the NIEHS site

MeSH Terms: Cell Line; DNA Replication*; DNA-Directed DNA Polymerase/metabolism*; DNA/biosynthesis*; Fanconi Anemia Complementation Group Proteins/metabolism; Humans; Hydroxyurea/metabolism; Proliferating Cell Nuclear Antigen/metabolism

Back
to Top