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Dna2 is involved in CA strand resection and nascent lagging strand completion at native yeast telomeres.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2013 Oct 11; Vol. 288 (41), pp. 29414-29. Date of Electronic Publication: 2013 Aug 20. - Publication Year :
- 2013
-
Abstract
- Post-replicational telomere end processing involves both extension by telomerase and resection to produce 3'-GT-overhangs that extend beyond the complementary 5'-CA-rich strand. Resection must be carefully controlled to maintain telomere length. At short de novo telomeres generated artificially by HO endonuclease in the G2 phase, we show that dna2-defective strains are impaired in both telomere elongation and sequential 5'-CA resection. At native telomeres in dna2 mutants, GT-overhangs do clearly elongate during late S phase but are shorter than in wild type, suggesting a role for Dna2 in 5'-CA resection but also indicating significant redundancy with other nucleases. Surprisingly, elimination of Mre11 nuclease or Exo1, which are complementary to Dna2 in resection of internal double strand breaks, does not lead to further shortening of GT-overhangs in dna2 mutants. A second step in end processing involves filling in of the CA-strand to maintain appropriate telomere length. We show that Dna2 is required for normal telomeric CA-strand fill-in. Yeast dna2 mutants, like mutants in DNA ligase 1 (cdc9), accumulate low molecular weight, nascent lagging strand DNA replication intermediates at telomeres. Based on this and other results, we propose that FEN1 is not sufficient and that either Dna2 or Exo1 is required to supplement FEN1 in maturing lagging strands at telomeres. Telomeres may be among the subset of genomic locations where Dna2 helicase/nuclease is essential for the two-nuclease pathway of primer processing on lagging strands.
- Subjects :
- Acetyltransferases genetics
Acetyltransferases metabolism
DNA Breaks, Double-Stranded
DNA Helicases metabolism
DNA Repair
DNA, Fungal metabolism
DNA, Single-Stranded genetics
DNA, Single-Stranded metabolism
Electrophoresis, Agar Gel
Endodeoxyribonucleases genetics
Endodeoxyribonucleases metabolism
Exodeoxyribonucleases genetics
Exodeoxyribonucleases metabolism
Flow Cytometry
Membrane Proteins genetics
Membrane Proteins metabolism
Mutation
Protein Binding
S Phase genetics
Saccharomyces cerevisiae metabolism
Saccharomyces cerevisiae Proteins metabolism
Telomere metabolism
DNA Helicases genetics
DNA, Fungal genetics
Saccharomyces cerevisiae genetics
Saccharomyces cerevisiae Proteins genetics
Telomere genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1083-351X
- Volume :
- 288
- Issue :
- 41
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 23963457
- Full Text :
- https://doi.org/10.1074/jbc.M113.472456