Telomere dynamics and fusion of critically shortened telomeres in plants lacking DNA ligase IV.
In the absence of the telomerase, telomeres undergo progressive shortening and are ultimately recruited into end-to-end chromosome fusions via the non-homologous end joining (NHEJ) double-strand break repair pathway. Previously, we showed that fusion of critically shortened telomeres in Arabidopsis proceeds with approximately the same efficiency in the presence or absence of KU70, a key component of NHEJ. Here we report that DNA ligase IV (LIG4) is also not essential for telomere joining. We observed only a modest decrease (3-fold) in the frequency of chromosome fusions in triple tert ku70 lig4 mutants versus tert ku70 or tert. Sequence analysis revealed that, relative to tert ku70, chromosome fusion junctions in tert ku70 lig4 mutants contained less microhomology and less telomeric DNA. These findings argue that the KU-LIG4 independent end-joining pathway is less efficient and mechanistically distinct from KU-independent NHEJ. Strikingly, in all the genetic backgrounds we tested, chromosome fusions are initiated when the shortest telomere in the population reaches approximately 1 kb, implying that this size represents a critical threshold that heralds a detrimental structural transition. These data reveal the transitory nature of telomere stability, and the robust and flexible nature of DNA repair mechanisms elicited by telomere dysfunction.
Heacock
Michelle L
ML
Department of Biochemistry and Biophysics, Texas A&M University 2128 TAMU, College Station, TX 77843-2128, USA.
Idol
Rachel A
RA
Friesner
Joanna D
JD
Britt
Anne B
AB
Shippen
Dorothy E
DE
D017360:Arabidopsis / Q000201:enzymology / Q000235:genetics*; D029681:Arabidopsis Proteins / Q000235:genetics; D032461:Chromosomes, Plant / Q000737:chemistry; D000072481:DNA Ligase ATP; D011088:DNA Ligases / Q000235:genetics / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics; D009154:Mutation; D010641:Phenotype; D017422:Sequence Analysis, DNA; D016615:Telomere / Q000737:chemistry* / Q000378:metabolism
D029681:Arabidopsis Proteins; D004268:DNA-Binding Proteins; C463462:KU70 protein, Arabidopsis; D011088:DNA Ligases; C525218:Lig4 protein, Arabidopsis; D000072481:DNA Ligase ATP