Prevention of unwanted recombination at damaged replication forks.

Current Genetics
Carl P LehmannJosé Antonio Tercero

Abstract

Homologous recombination is essential for the maintenance of genome integrity but must be strictly controlled to avoid dangerous outcomes that produce the opposite effect, genomic instability. During unperturbed chromosome replication, recombination is globally inhibited at ongoing DNA replication forks, which helps to prevent deleterious genomic rearrangements. This inhibition is carried out by Srs2, a helicase that binds to SUMOylated PCNA and has an anti-recombinogenic function at replication forks. However, at damaged stalled forks, Srs2 is counteracted and DNA lesion bypass can be achieved by recombination-mediated template switching. In budding yeast, template switching is dependent on Rad5. In the absence of this protein, replication forks stall in the presence of DNA lesions and cells die. Recently, we showed that in cells lacking Rad5 that are exposed to DNA damage or replicative stress, elimination of the conserved Mgs1/WRNIP1 ATPase allows an alternative mode of DNA damage bypass that is driven by recombination and facilitates completion of chromosome replication and cell viability. We have proposed that Mgs1 is important to prevent a potentially harmful salvage pathway of recombination at damaged stalled forks. In t...Continue Reading

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Citations

Aug 26, 2020·FEMS Microbiology Reviews·Matan ArbelMartin Kupiec
Nov 26, 2020·Current Genetics·Katrin Paeschke, Peter Burkovics
Mar 22, 2021·Nucleic Acids Research·Lewis J BainbridgeAidan J Doherty
Jul 21, 2021·International Journal of Radiation Biology·Jac A NickoloffRobert Hromas

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