Multiple DNA associated processes such as DNA repair, replication and recombination are crucial for the maintenance of genome integrity. Here, we show a novel interaction between the transcription elongation factor Bur1-Bur2 and replication protein A (RPA), the eukaryotic single-stranded DNA binding protein with functions in DNA repair, recombination, and replication. Bur1 interacts via its C-terminal domain with RPA, and bur1-ΔC mutants show a deregulated DNA damage response accompanied by increased sensitivity to DNA damage and replication stress as well as increased levels of persisting Rad52 foci. Interestingly, the DNA damage sensitivity of an rfa1 mutant is suppressed by bur1 mutation further underscoring a functional link between these two protein complexes. Taken together, the transcription elongation factor Bur1-Bur2 interacts with RPA and maintains genome integrity during DNA replication stress.