DNA Polymerase λ Can Elongate on Dna Substrates Mimicking Non-Homologous End Joining and Interact With XRCC4-Ligase IV Complex
Document Type
Article
Publication Date
10-29-2004
Description
Non-homologous end joining (NHEJ) is one of two pathways responsible for the repair of double-strand breaks in eukaryotic cells. The mechanism involves the alignment of broken DNA ends with minimal homology, fill in of short gaps by DNA polymerase(s), and ligation by XRCC4-DNA ligase IV complex. The gap-filling polymerase has not yet been positively identified, but recent biochemical studies have implicated DNA polymerase λ (pol λ), a novel DNA polymerase that has been assigned to the pol X family, in this process. Here we demonstrate that purified pol λ can efficiently catalyze gap-filling synthesis on DNA substrates mimicking NHEJ. By designing two truncated forms of pol λ, we also show that the unique proline-rich region in pol λ plays a role in limiting strand displacement synthesis, a feature that may help its participation in in vivo NHEJ. Moreover, pol λ interacts with XRCC4-DNA ligase IV via its N-terminal BRCT domain and the interaction stimulates the DNA synthesis activity of pol λ. Taken together, these data strongly support that pol λ functions in DNA polymerization events during NHEJ.
Citation Information
Fan, Wei; and Wu, Xiaoming. 2004. DNA Polymerase λ Can Elongate on Dna Substrates Mimicking Non-Homologous End Joining and Interact With XRCC4-Ligase IV Complex. Biochemical and Biophysical Research Communications. Vol.323(4). 1328-1333. https://doi.org/10.1016/j.bbrc.2004.09.002 PMID: 15451442 ISSN: 0006-291X