Unknown

Dataset Information

0

TRF2/RAP1 and DNA-PK mediate a double protection against joining at telomeric ends.


ABSTRACT: DNA-dependent protein kinase (DNA-PK) is a double-strand breaks repair complex, the subunits of which (KU and DNA-PKcs) are paradoxically present at mammalian telomeres. Telomere fusion has been reported in cells lacking these proteins, raising two questions: how is DNA-PK prevented from initiating classical ligase IV (LIG4)-dependent non-homologous end-joining (C-NHEJ) at telomeres and how is the backup end-joining (EJ) activity (B-NHEJ) that operates at telomeres under conditions of C-NHEJ deficiency controlled? To address these questions, we have investigated EJ using plasmid substrates bearing double-stranded telomeric tracks and human cell extracts with variable C-NHEJ or B-NHEJ activity. We found that (1) TRF2/RAP1 prevents C-NHEJ-mediated end fusion at the initial DNA-PK end binding and activation step and (2) DNA-PK counteracts a potent LIG4-independent EJ mechanism. Thus, telomeres are protected against EJ by a lock with two bolts. These results account for observations with mammalian models and underline the importance of alternative non-classical EJ pathways for telomere fusions in cells.

SUBMITTER: Bombarde O 

PROVIDER: S-EPMC2876953 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC4357705 | biostudies-literature
| S-EPMC5808845 | biostudies-literature
| S-EPMC3753591 | biostudies-literature
| S-EPMC2666026 | biostudies-literature
| S-EPMC544002 | biostudies-literature
2013-06-01 | GSE46209 | GEO
2013-06-01 | E-GEOD-46209 | biostudies-arrayexpress
| S-EPMC23689 | biostudies-literature
| S-EPMC10240986 | biostudies-literature
| S-EPMC3247945 | biostudies-literature