Identification of a novel REV1-interacting motif necessary for DNA polymerase κ function

Eiji Ohashi, Tomo Hanafusa, Keijiro Kamei, Ihnyoung Song, Junya Tomida, Hiroshi Hashimoto, Cyrus Vaziri, Haruo Ohmori

Research output: Contribution to journalArticlepeer-review

77 Citations (Scopus)

Abstract

When a replicative DNA polymerase (Pol) is stalled by damaged DNA, a "polymerase switch" recruits specialized translesion synthesis (TLS) DNA polymerase(s) to sites of damage. Mammalian cells have several TLS DNA polymerases, including the four Y-family enzymes (Polη, Polι, Polκ and REV1) that share multiple primary sequence motifs, but show preferential bypass of different DNA lesions. REV1 interacts with Polη, Polι, and Polκ and therefore appears to play a central role during TLS in vivo. Here we have investigated the molecular basis for interactions between REV1 and Polκ. We have identified novel REV1-interacting regions (RIRs) present in Polκ, Polι and Polε. Within the RIRs, the presence of two consecutive phenylalanines (FF) is essential for REV1-binding. The consensus sequence for REV1-binding is denoted by x-x-x-F-F-y-y-y-y (x, no specific residue and y, no specific residue but not proline). Our results identify structural requirements that are necessary for FF-flanking residues to confer interactions with REV1. A Polκ mutant lacking REV1-binding activity did not complement the genotoxin-sensitivity of Polk-null mouse embryonic fibroblast cells, thereby demonstrating that the REV1-interaction is essential for Polκ function in vivo.

Original languageEnglish
Pages (from-to)101-111
Number of pages11
JournalGenes to Cells
Volume14
Issue number2
DOIs
Publication statusPublished - 2009
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Genetics
  • Cell Biology

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