Abstract
Cancer cells require mechanisms to maintain telomeres. Most use telomerase, but 5% to 20% of tumors use alternative lengthening of telomeres (ALT), a telomerase-independent mechanism that seems to depend on recombination. ALT is characterized by amplification of telomere TTAGGG repeats to lengths beyond 50 kb, by elevated rates of telomere recombination, and by nuclear structures called ALT-associated promyelocytic leukemia bodies. In Saccharomyces cerevisiae, survivors of telomerase inactivation also use recombination to maintain telomeres. There are two types of survivors, which differ in telomere structure. The first possesses telomere repeats and the Y′ subtelomeric element amplified together as a tandem array at chromosome termini (type I), and the other possesses amplification of telomeric repeats alone (type II), similar to previously described human ALT cells. Here, we describe the first human ALT cell line having "tandem array" telomeres with a structure similar to that of type I yeast survivors. The chromosome termini consist of a repeat unit containing ∼2.5 kb of SV40 DNA and a variable amount of TTAGGG sequence repeated in tandem an average of 10 to 20 times. Similar to previously described ALT cells, they show evidence of telomere recombination, but unlike standard ALT cells, they lack ALT-associated promyelocytic leukemia bodies and their telomeres are transcribed. These findings have implications for the pathogenesis and diagnosis of cancer.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2730-2737 |
| Number of pages | 8 |
| Journal | Cancer Research |
| Volume | 65 |
| Issue number | 7 |
| DOIs | |
| State | Published - Apr 1 2005 |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
A novel telomere structure in a human alternative lengthening of telomeres cell line. / Marciniak, Robert A; Cavazos, David; Montellano, Richard; Chen, Qijun; Guarente, Leonard; Johnson, F. Brad.
In: Cancer Research, Vol. 65, No. 7, 01.04.2005, p. 2730-2737.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - A novel telomere structure in a human alternative lengthening of telomeres cell line
AU - Marciniak, Robert A
AU - Cavazos, David
AU - Montellano, Richard
AU - Chen, Qijun
AU - Guarente, Leonard
AU - Johnson, F. Brad
PY - 2005/4/1
Y1 - 2005/4/1
N2 - Cancer cells require mechanisms to maintain telomeres. Most use telomerase, but 5% to 20% of tumors use alternative lengthening of telomeres (ALT), a telomerase-independent mechanism that seems to depend on recombination. ALT is characterized by amplification of telomere TTAGGG repeats to lengths beyond 50 kb, by elevated rates of telomere recombination, and by nuclear structures called ALT-associated promyelocytic leukemia bodies. In Saccharomyces cerevisiae, survivors of telomerase inactivation also use recombination to maintain telomeres. There are two types of survivors, which differ in telomere structure. The first possesses telomere repeats and the Y′ subtelomeric element amplified together as a tandem array at chromosome termini (type I), and the other possesses amplification of telomeric repeats alone (type II), similar to previously described human ALT cells. Here, we describe the first human ALT cell line having "tandem array" telomeres with a structure similar to that of type I yeast survivors. The chromosome termini consist of a repeat unit containing ∼2.5 kb of SV40 DNA and a variable amount of TTAGGG sequence repeated in tandem an average of 10 to 20 times. Similar to previously described ALT cells, they show evidence of telomere recombination, but unlike standard ALT cells, they lack ALT-associated promyelocytic leukemia bodies and their telomeres are transcribed. These findings have implications for the pathogenesis and diagnosis of cancer.
AB - Cancer cells require mechanisms to maintain telomeres. Most use telomerase, but 5% to 20% of tumors use alternative lengthening of telomeres (ALT), a telomerase-independent mechanism that seems to depend on recombination. ALT is characterized by amplification of telomere TTAGGG repeats to lengths beyond 50 kb, by elevated rates of telomere recombination, and by nuclear structures called ALT-associated promyelocytic leukemia bodies. In Saccharomyces cerevisiae, survivors of telomerase inactivation also use recombination to maintain telomeres. There are two types of survivors, which differ in telomere structure. The first possesses telomere repeats and the Y′ subtelomeric element amplified together as a tandem array at chromosome termini (type I), and the other possesses amplification of telomeric repeats alone (type II), similar to previously described human ALT cells. Here, we describe the first human ALT cell line having "tandem array" telomeres with a structure similar to that of type I yeast survivors. The chromosome termini consist of a repeat unit containing ∼2.5 kb of SV40 DNA and a variable amount of TTAGGG sequence repeated in tandem an average of 10 to 20 times. Similar to previously described ALT cells, they show evidence of telomere recombination, but unlike standard ALT cells, they lack ALT-associated promyelocytic leukemia bodies and their telomeres are transcribed. These findings have implications for the pathogenesis and diagnosis of cancer.
UR - http://www.scopus.com/inward/record.url?scp=16844379374&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=16844379374&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-04-2888
DO - 10.1158/0008-5472.CAN-04-2888
M3 - Article
C2 - 15805272
AN - SCOPUS:16844379374
VL - 65
SP - 2730
EP - 2737
JO - Cancer Research
JF - Cancer Research
SN - 0008-5472
IS - 7
ER -