title: Noncatalytic, N-terminal Domains of DNA Polymerase Lambda Affect Its Cellular Localization and DNA Damage Response.
abstract: Specialized DNA polymerases, such as DNA polymerase lambda (Polλ), are important players in DNA damage tolerance and repair pathways. Knowing how DNA polymerases are regulated and recruited to sites of DNA damage is imperative to understanding these pathways. Recent work has suggested that Polλ plays a role in several distinct DNA damage tolerance and repair pathways. In this paper, we report previously unknown roles of the N-terminal domains of human Polλ for modulating its involvement in DNA damage tolerance and repair. By using Western blot analysis, fluorescence microscopy, and cell survival assays, we found that the BRCA1 C-terminal (BRCT) and proline/serine-rich (PSR) domains of Polλ affect its cellular localization and DNA damage responses. The nuclear localization signal (NLS) of Polλ was necessary to overcome the impediment of its nuclear localization caused by its BRCT and PSR domains. Induction of DNA damage resulted in recruitment of Polλ to chromatin, which was controlled by its BRCT and PSR domains. In addition, the presence of both domains was required for Polλ-mediated tolerance of oxidative DNA damage but not DNA methylation damage. These findings suggest that the N-terminal domains of Polλ are important for regulating its responses to DNA damage.
authors.affiliation: Department of Chemistry and Biochemistry and ‡The Ohio State Biochemistry Program, The Ohio State University , Columbus, Ohio 43210, United States.
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Stephenson
authors.affiliation: Department of Chemistry and Biochemistry and ‡The Ohio State Biochemistry Program, The Ohio State University , Columbus, Ohio 43210, United States.
authors.forename: David J
authors.initials: DJ
authors.lastname: Taggart
authors.affiliation: Department of Chemistry and Biochemistry and ‡The Ohio State Biochemistry Program, The Ohio State University , Columbus, Ohio 43210, United States.
authors.forename: Zucai
authors.identifier: 0000-0003-3871-3420
authors.initials: Z
authors.lastname: Suo
mesh_terms: D000818:Animals; D002384:Catalysis; D002460:Cell Line; D002467:Cell Nucleus / Q000201:enzymology; D003001:Cloning, Molecular; D004249:DNA Damage; D019951:DNA Polymerase beta / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice
chemical_list: C415367:DNA polymerase beta2; D019951:DNA Polymerase beta