Eukaryotic translesion synthesis: Choosing the right tool for the job

DNA Repair
Kyle T Powers, M T Washington

Abstract

Normal DNA replication is blocked by DNA damage in the template strand. Translesion synthesis is a major pathway for overcoming these replication blocks. In this process, multiple non-classical DNA polymerases are thought to form a complex at the stalled replication fork that we refer to as the mutasome. This hypothetical multi-protein complex is structurally organized by the replication accessory factor PCNA and the non-classical polymerase Rev1. One of the non-classical polymerases within this complex then catalyzes replication through the damage. Each non-classical polymerase has one or more cognate lesions, which the enzyme bypasses with high accuracy and efficiency. Thus, the accuracy and efficiency of translesion synthesis depends on which non-classical polymerase is chosen to bypass the damage. In this review article, we discuss how the most appropriate polymerase is chosen. In so doing, we examine the structural motifs that mediate the protein interactions in the mutasome; the multiple architectures that the mutasome can adopt, such as PCNA tool belts and Rev1 bridges; the intrinsically disordered regions that tether the polymerases to PCNA and to one another; and the kinetic selection model in which the most appropriat...Continue Reading

Citations

Feb 6, 2020·Genes·Brittany M RipleyM Todd Washington
Feb 2, 2020·Applied and Environmental Microbiology·Rui YaoJing Wu
Jul 8, 2020·Nucleic Acids Research·Rachel Bezalel-BuchPeter M Burgers
Oct 2, 2020·Proceedings of the National Academy of Sciences of the United States of America·Tyler M WeaverBret D Freudenthal
Oct 7, 2020·International Journal of Molecular Sciences·Mateusz KciukRenata Kontek
Jan 9, 2021·Expert Opinion on Therapeutic Targets·Sumeet NayakSharon B Cantor
Feb 2, 2021·The Journal of Investigative Dermatology·Paulo F L da Silva, Björn Schumacher
Jul 15, 2020·DNA Repair·Katherine M Amidon, Brandt F Eichman
May 1, 2021·International Journal of Molecular Sciences·Domenico MaioranoJean-Sébastien Hoffmann
May 11, 2021·Seminars in Cell & Developmental Biology·Christine M KondratickMaria Spies
May 15, 2021·The Plant Journal : for Cell and Molecular Biology·Maherun NisaCécile Raynaud

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