Strand-specific postreplicative processing of mammalian telomeres.
Telomeres are specialized nucleoprotein structures that stabilize the ends of linear eukaryotic chromosomes. In mammalian cells, abrogation of telomeric repeat binding factor TRF2 or DNA-dependent protein kinase (DNA-PK) activity causes end-to-end chromosomal fusion, thus establishing an essential role for these proteins in telomere function. Here we show that TRF2-mediated end-capping occurs after telomere replication. The postreplicative requirement for TRF2 and DNA-PKcs, the catalytic subunit of DNA-PK, is confined to only half of the telomeres, namely, those that were produced by leading-strand DNA synthesis. These results demonstrate a crucial difference in postreplicative processing of telomeres that is linked to their mode of replication.
Bailey
S M
SM
Bioscience Division, Los Alamos National Laboratory, Los Alamos, NM 87544, USA.
Cornforth
M N
MN
Kurimasa
A
A
Chen
D J
DJ
Goodwin
E H
EH
D000818:Animals; D002455:Cell Division; D002460:Cell Line; D002842:Chromatids / Q000502:physiology / Q000648:ultrastructure; D002875:Chromosomes / Q000502:physiology / Q000648:ultrastructure; D004261:DNA Replication; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D017403:In Situ Hybridization; D051379:Mice; D008938:Mitosis; D009154:Mutation; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency / Q000378:metabolism; D016615:Telomere / Q000378:metabolism*; D035341:Telomeric Repeat Binding Protein 2; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D035341:Telomeric Repeat Binding Protein 2; D051747:DNA-Activated Protein Kinase; C497263:PRKDC protein, human; D017346:Protein Serine-Threonine Kinases