Skip Navigation

Publication Detail

Title: Human Mre11/human Rad50/Nbs1 and DNA ligase IIIalpha/XRCC1 protein complexes act together in an alternative nonhomologous end joining pathway.

Authors: Della-Maria, Julie; Zhou, Yi; Tsai, Miaw-Sheue; Kuhnlein, Jeff; Carney, James P; Paull, Tanya T; Tomkinson, Alan E

Published In J Biol Chem, (2011 Sep 30)

Abstract: Recent studies have implicated a poorly defined alternative pathway of nonhomologous end joining (alt-NHEJ) in the generation of large deletions and chromosomal translocations that are frequently observed in cancer cells. Here, we describe an interaction between two factors, hMre11/hRad50/Nbs1 (MRN) and DNA ligase IIIα/XRCC1, that have been linked with alt-NHEJ. Expression of DNA ligase IIIα and the association between MRN and DNA ligase IIIα/XRCC1 are altered in cell lines defective in the major NHEJ pathway. Most notably, DNA damage induced the association of these factors in DNA ligase IV-deficient cells. MRN interacts with DNA ligase IIIα/XRCC1, stimulating intermolecular ligation, and together these proteins join incompatible DNA ends in a reaction that mimics alt-NHEJ. Thus, our results provide novel mechanistic insights into the alt-NHEJ pathway that not only contributes to genome instability in cancer cells but may also be a therapeutic target.

PubMed ID: 21816818 Exiting the NIEHS site

MeSH Terms: Acid Anhydride Hydrolases; Cell Cycle Proteins/genetics; Cell Cycle Proteins/metabolism*; Cell Line, Tumor; DNA Damage/physiology; DNA Ligase ATP; DNA Ligases/genetics; DNA Ligases/metabolism*; DNA Repair Enzymes/genetics; DNA Repair Enzymes/metabolism*; DNA Repair/physiology*; DNA-Binding Proteins/genetics; DNA-Binding Proteins/metabolism*; Genomic Instability/physiology; Humans; MRE11 Homologue Protein; Multiprotein Complexes/genetics; Multiprotein Complexes/metabolism*; Nuclear Proteins/genetics; Nuclear Proteins/metabolism*; Poly-ADP-Ribose Binding Proteins; X-ray Repair Cross Complementing Protein 1; Xenopus Proteins

Back
to Top