# Characterizing the LINE-1 Retrotransposition-Replication Conflict

> **NIH NIH R01** · DANA-FARBER CANCER INST · 2021 · $404,888

## Abstract

Project Summary
Much of our genome is made up of interspersed repeats derived from the activities of mobile genetic elements.
There are subsets of these sequences that become activated in cancers. Our research lab and others have
shown that nearly half of cancers fail to restrain long interspersed element-1 (LINE-1, L1) sequences. L1 is an
active retrotransposon that codes for two proteins, an RNA binding protein (ORF1p) and a protein with
endonuclease and reverse transcriptase activities (ORF2p). Paradoxically, though these proteins are
pervasively expressed in many human cancers, they inhibit cell growth in culture. We have exciting new data
from genome-wide knockout screens demonstrating how tumor suppressor gene mutations found in cancers
enable them to survive and grow despite their expression of L1. More importantly, these screens have also
identified genes that become essential in cells coping with L1 expression. These synthetic lethal genes
represent unique molecular vulnerabilities for L1(+) cells. L1(+) cells require specific DNA repair pathways,
effective replication stress signaling pathways, and replication fork restart capabilities. Here, we will test the
hypothesis that these pathways are required to eliminate L1 insertion intermediates and prevent collisions
between these intermediates and DNA replication forks. This project will increase our understanding of how
cancer cells replicate their DNA. It could lay a foundation to leverage L1-associated DNA replication stress to
limit cancer cell growth.

## Key facts

- **NIH application ID:** 10215445
- **Project number:** 5R01CA240816-02
- **Recipient organization:** DANA-FARBER CANCER INST
- **Principal Investigator:** KATHLEEN H BURNS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $404,888
- **Award type:** 5
- **Project period:** 2020-07-15 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10215445

## Citation

> US National Institutes of Health, RePORTER application 10215445, Characterizing the LINE-1 Retrotransposition-Replication Conflict (5R01CA240816-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10215445. Licensed CC0.

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