# Identification of Essential Factors for the Alternative Lengthening of Telomeres Pathway

> **NIH NIH F31** · SCRIPPS RESEARCH INSTITUTE, THE · 2020 · $6,320

## Abstract

ABSTRACT
Telomeres consist of TTAGGG repeats bound by protein complexes that serve to protect the natural
ends of linear chromosomes and ensure genome stability. Due to the end replication problem,
telomeres progressively shorten with each cellular division until they become critically short, resulting
in cellular senescence or apoptosis. A universal feature of human cancer cells is the ability to bypass
this proliferation barrier by engaging a telomere elongation mechanism, which is most often the
expression of the reverse transcriptase telomerase. However, a significant portion of cancer cells
(approx 10-15%) utilize a telomerase-independent pathway named the Alternative Lengthening of
Telomeres (ALT) pathway that relies on homologous recombination between telomeric sequences to
extend telomeres and evade replicative arrest. Cancer cells that utilize ALT are characterized by
heterogeneous telomere lengths, extrachromosomal telomeric DNA and the presence of
promyelocytic leukemia (PML) bodies at telomeres. Although the ALT pathway has been the subject
of intense investigation, the mechanism by which it occurs is still incompletely understood. In order to
shed light on the ALT pathway, we will employ CRISPR/Cas9 to generate genetic knockouts of the
known ALT-associated factors PML and SUMO2 to assess their essentiality in ALT activity.
Additionally, we will use CRISPR/Cas9 to perform a genome-wide gRNA knockout screen to identify
novel factors required for ALT. In this way, we will identify factors essential for ALT to expand our
understanding of this telomere maintenance mechanism and reveal potential therapeutic targets for
the treatment of ALT cancers.

## Key facts

- **NIH application ID:** 9891984
- **Project number:** 5F31CA228283-03
- **Recipient organization:** SCRIPPS RESEARCH INSTITUTE, THE
- **Principal Investigator:** Taylor Kristine Loe
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $6,320
- **Award type:** 5
- **Project period:** 2018-04-01 → 2020-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9891984

## Citation

> US National Institutes of Health, RePORTER application 9891984, Identification of Essential Factors for the Alternative Lengthening of Telomeres Pathway (5F31CA228283-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9891984. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*