Structural highlights
Function
[CDC13_YEAST] Single-stranded telomeric DNA-binding protein that regulates telomere replication. Has a role in both positive and negative regulation. Promotes [TG(1-3)] strand lengthening via interaction with EST1. Promotes [C(1-3)A] strand re-synthesis by DNA polymerase alpha via interaction with POL1. Negatively regulates telomere elongation of the G strand via binding with STN1 thereby inhibiting telomerase activity.[1] [2] [3]
Publication Abstract from PubMed
Cdc13 is an essential yeast protein required for telomere length regulation and genome stability. It does so via its telomere-capping properties and by regulating telomerase access to the telomeres. The crystal structure of the Saccharomyces cerevisiae Cdc13 domain located between the recruitment and DNA binding domains reveals an oligonucleotide-oligosaccharide binding fold (OB2) with unusually long loops extending from the core of the protein. These loops are involved in extensive interactions between two Cdc13 OB2 folds leading to stable homodimerization. Interestingly, the functionally impaired cdc13-1 mutation inhibits OB2 dimerization. Biochemical assays indicate OB2 is not involved in telomeric DNA or Stn1 binding. However, disruption of the OB2 dimer in full-length Cdc13 affects Cdc13-Stn1 association, leading to telomere length deregulation, increased temperature sensitivity, and Stn1 binding defects. We therefore propose that dimerization of the OB2 domain of Cdc13 is required for proper Cdc13, Stn1, Ten1 (CST) assembly and productive telomere capping.
Cdc13 OB2 Dimerization Required for Productive Stn1 Binding and Efficient Telomere Maintenance.,Mason M, Wanat JJ, Harper S, Schultz DC, Speicher DW, Johnson FB, Skordalakes E Structure. 2012 Nov 20. pii: S0969-2126(12)00386-3. doi:, 10.1016/j.str.2012.10.012. PMID:23177925[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Chandra A, Hughes TR, Nugent CI, Lundblad V. Cdc13 both positively and negatively regulates telomere replication. Genes Dev. 2001 Feb 15;15(4):404-14. PMID:11230149 doi:10.1101/gad.861001
- ↑ Meier B, Driller L, Jaklin S, Feldmann HM. New function of CDC13 in positive telomere length regulation. Mol Cell Biol. 2001 Jul;21(13):4233-45. PMID:11390652 doi:10.1128/MCB.21.13.4233-4245.2001
- ↑ Qi H, Zakian VA. The Saccharomyces telomere-binding protein Cdc13p interacts with both the catalytic subunit of DNA polymerase alpha and the telomerase-associated est1 protein. Genes Dev. 2000 Jul 15;14(14):1777-88. PMID:10898792
- ↑ Mason M, Wanat JJ, Harper S, Schultz DC, Speicher DW, Johnson FB, Skordalakes E. Cdc13 OB2 Dimerization Required for Productive Stn1 Binding and Efficient Telomere Maintenance. Structure. 2012 Nov 20. pii: S0969-2126(12)00386-3. doi:, 10.1016/j.str.2012.10.012. PMID:23177925 doi:http://dx.doi.org/10.1016/j.str.2012.10.012
