# THREE-DIMENSIONAL STRUCTURE OF THE ENDS OF CHROMOSOMES

> **NIH NIH R01** · UNIVERSITY OF COLORADO · 1993 · $182,324

## Abstract

The overall goal of this project is to learn about telomere structure and
function by determining the x-ray crystal structures of nucleoprotein
complexes that compose telomeres.  Currently, our efforts ar focused on
two cloned and characterized proteins that are known to be components of
telomeres in vivo: (i) the telomere binding protein from Oxytricha nova
which interacts with single-strand DNA at the very ends of telomeres and
(ii) RAP1 from yeast which interacts with the double-stranded DNA region
of telomeres and has been shown to participate in regulating telomere
length.

The telomere binding protein from Oxytricha nova interacts with single-
strand DNA (sequence TTTTGGGGTTTTGGGG) that occurs at the very ends of
telomeres.  The telomere binding protein consists of two subunits; a 56
Kd alpha-subunit that interacts single-strand (TTTTGGGG)n DNA in a
sequence specific manner and a 41 KD beta-subunit that alters the DNA in
a sequence specific manner and a 41 KD beta-subunit that alters the DNA
binding properties of the alpha-subunit.  The alpha- and beta-subunits
do not interact in solution in the absence of DNA, but together with
(TTTTGGGG)n DNA they form a very tight ternary complex containing the
alpha-subunit, the beta-subunit, and DNA.  We have obtained crystals of
(i) the alpha-subunit complexed with TTTTGGGG DNA that diffract to 2.7A
resolution, (ii) the beta-subunit in th presence of GGGG DNA, and (iii)
the entire ternary complex containing the alpha-subunit, the beta-
subunit, and GGGGTTTTGGGG DNA that diffract to at least 3 A resolution.
We are now poised for a very detailed look at the telomere binding
protein-DNA complex which will greatly enhance our understanding of how
the two subunits of this protein interact with DNA and with each other
to form the nucleoprotein complex that caps the ends of chromosomes.

RAP1 is associated with yeast telomeres in vivo and is necessary for
proper regulation of telomere length.  Mutations in this protein give
rise to either elongated or shortened telomeres.  RAP1 is a sequence-
specific double-stranded DNA binding protein that interacts with the
sequence ACACCCACACACC which occurs every 30-40 base pairs in yeast
telomeres.  Interestingly, RAP1 has been shown to bend DNA such that it
may give rise to a higher order structure in yeast telomeres.  We have
begun efforts to obtain large quantities of RAP1 for crystallization and
structure determination.

That improper maintenance of telomere length and structure limits a cells
ability to divide and results in senescence has been clearly established.
Indeed, it is proposed that telomeres play a critical role in cell
division and in the "senescence program:\" in higher eukaryotes.
Understanding the structure of the nucleoprotein complexes that compose
telomeres will lead to a better overall understanding of the structure
and function of telomeres.

## Key facts

- **NIH application ID:** 3123538
- **Project number:** 1R01AG011636-01
- **Recipient organization:** UNIVERSITY OF COLORADO
- **SAM.gov UEI:** SPVKK1RC2MZ3
- **Principal Investigator:** STEVE C SCHULTZ
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $182,324
- **Award type:** 1
- **Project period:** 1993-09-30 → 1998-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3123538

## Citation

> US National Institutes of Health, RePORTER application 3123538, THREE-DIMENSIONAL STRUCTURE OF THE ENDS OF CHROMOSOMES (1R01AG011636-01). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3123538. Licensed CC0.

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