Separate Roles of Structured and Unstructured Regions of Y-family DNA Polymerases
Overview
Affiliations
All organisms have multiple DNA polymerases specialized for translesion DNA synthesis (TLS) on damaged DNA templates. Mammalian TLS DNA polymerases include Pol eta, Pol iota, Pol kappa, and Rev1 (all classified as "Y-family" members) and Pol zeta (a "B-family" member). Y-family DNA polymerases have highly structured catalytic domains; however, some of these proteins adopt different structures when bound to DNA (such as archaeal Dpo4 and human Pol kappa), while others maintain similar structures independently of DNA binding (such as archaeal Dbh and Saccharomyces cerevisiae Pol eta). DNA binding-induced structural conversions of TLS polymerases depend on flexible regions present within the catalytic domains. In contrast, noncatalytic regions of Y-family proteins, which contain multiple domains and motifs for interactions with other proteins, are predicted to be mostly unstructured, except for short regions corresponding to ubiquitin-binding domains. In this review we discuss how the organization of structured and unstructured regions in TLS polymerases is relevant to their regulation and function during lesion bypass.
Verschuren J, van Schendel R, van Bostelen I, Verkennis A, Knipscheer P, Tijsterman M Nat Commun. 2025; 16(1):2495.
PMID: 40082407 PMC: 11906846. DOI: 10.1038/s41467-025-57764-z.
Implications of Translesion DNA Synthesis Polymerases on Genomic Stability and Human Health.
Venkadakrishnan J, Lahane G, Dhar A, Xiao W, Bhat K, Pandita T Mol Cell Biol. 2023; 43(8):401-425.
PMID: 37439479 PMC: 10448981. DOI: 10.1080/10985549.2023.2224199.
Wu W, Barwacz S, Bhowmick R, Lundgaard K, Goncalves Dinis M, Clausen M Nat Commun. 2023; 14(1):706.
PMID: 36759509 PMC: 9911744. DOI: 10.1038/s41467-023-35992-5.
Post-Translational Modifications of PCNA: Guiding for the Best DNA Damage Tolerance Choice.
Belli G, Colomina N, Castells-Roca L, Lorite N J Fungi (Basel). 2022; 8(6).
PMID: 35736104 PMC: 9225081. DOI: 10.3390/jof8060621.
Recent Advances in Understanding the Structures of Translesion Synthesis DNA Polymerases.
Ling J, Frevert Z, Washington M Genes (Basel). 2022; 13(5).
PMID: 35627300 PMC: 9141541. DOI: 10.3390/genes13050915.