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
The essential yeast protein Cdc13 facilitates chromosome end replication by recruiting telomerase to telomeres, and together with its interacting partners Stn1 and Ten1, it protects chromosome ends from nucleolytic attack, thus contributing to genome integrity. Although Cdc13 has been studied extensively, the precise role of its N-terminal domain (Cdc13N) in telomere length regulation remains unclear. Here we present a structural, biochemical, and functional characterization of Cdc13N. The structure reveals that this domain comprises an oligonucleotide/oligosaccharide binding (OB) fold and is involved in Cdc13 dimerization. Biochemical data show that Cdc13N weakly binds long, single-stranded, telomeric DNA in a fashion that is directly dependent on domain oligomerization. When introduced into full-length Cdc13 in vivo, point mutations that prevented Cdc13N dimerization or DNA binding caused telomere shortening or lengthening, respectively. The multiple DNA binding domains and dimeric nature of Cdc13 offer unique insights into how it coordinates the recruitment and regulation of telomerase access to the telomeres.
Cdc13 N-terminal dimerization, DNA binding, and telomere length regulation.,Mitchell MT, Smith JS, Mason M, Harper S, Speicher DW, Johnson FB, Skordalakes E Mol Cell Biol. 2010 Nov;30(22):5325-34. Epub 2010 Sep 13. PMID:20837709[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
- ↑ Mitchell MT, Smith JS, Mason M, Harper S, Speicher DW, Johnson FB, Skordalakes E. Cdc13 N-terminal dimerization, DNA binding, and telomere length regulation. Mol Cell Biol. 2010 Nov;30(22):5325-34. Epub 2010 Sep 13. PMID:20837709 doi:10.1128/MCB.00515-10
