title: DNA damage-induced phosphorylation of TRF2 is required for the fast pathway of DNA double-strand break repair.
abstract: Protein kinases of the phosphatidylinositol 3-kinase-like kinase family, originally known to act in maintaining genomic integrity via DNA repair pathways, have been shown to also function in telomere maintenance. Here we focus on the functional role of DNA damage-induced phosphorylation of the essential mammalian telomeric DNA binding protein TRF2, which coordinates the assembly of the proteinaceous cap to disguise the chromosome end from being recognized as a double-stand break (DSB). Previous results suggested a link between the transient induction of human TRF2 phosphorylation at threonine 188 (T188) by the ataxia telangiectasia mutated protein kinase (ATM) and the DNA damage response. Here, we report evidence that X-ray-induced phosphorylation of TRF2 at T188 plays a role in the fast pathway of DNA DSB repair. These results connect the highly transient induction of human TRF2 phosphorylation to the DNA damage response machinery. Thus, we find that a protein known to function in telomere maintenance, TRF2, also plays a functional role in DNA DSB repair.
authors.affiliation: Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
authors.forename: Nazmul
authors.initials: N
authors.lastname: Huda
authors.forename: Hiromi
authors.initials: H
authors.lastname: Tanaka
authors.forename: Marc S
authors.initials: MS
authors.lastname: Mendonca
authors.forename: David
authors.initials: D
authors.lastname: Gilley
mesh_terms: D017209:Apoptosis / Q000502:physiology; D002460:Cell Line / Q000378:metabolism / Q000528:radiation effects; D053903:DNA Breaks, Double-Stranded; D004249:DNA Damage; D004260:DNA Repair; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009154:Mutation; D010766:Phosphorylation; D016615:Telomere / Q000378:metabolism; D035341:Telomeric Repeat Binding Protein 2 / Q000235:genetics / Q000378:metabolism*; D013912:Threonine / Q000378:metabolism; D014965:X-Rays
chemical_list: C468783:H2AX protein, human; D006657:Histones; D035341:Telomeric Repeat Binding Protein 2; D013912:Threonine