Characterizing the LINE-1 Retrotransposition-Replication Conflict

表征 LINE-1 逆转录转座-复制冲突

基本信息

  • 批准号:
    10634604
  • 负责人:
  • 金额:
    $ 39.68万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2020
  • 资助国家:
    美国
  • 起止时间:
    2020-07-15 至 2025-06-30
  • 项目状态:
    未结题

项目摘要

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.
项目总结

项目成果

期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
LINE-1 retrotransposition and its deregulation in cancers: implications for therapeutic opportunities.
  • DOI:
    10.1101/gad.351051.123
  • 发表时间:
    2023-12-26
  • 期刊:
  • 影响因子:
    10.5
  • 作者:
    Mendez-Dorantes, Carlos;Burns, Kathleen H
  • 通讯作者:
    Burns, Kathleen H
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KATHLEEN H BURNS其他文献

KATHLEEN H BURNS的其他文献

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{{ truncateString('KATHLEEN H BURNS', 18)}}的其他基金

Consequences of retrotransposition on genome integrity
逆转录转座对基因组完整性的影响
  • 批准号:
    10736406
  • 财政年份:
    2023
  • 资助金额:
    $ 39.68万
  • 项目类别:
Characterizing the LINE-1 Retrotransposition-Replication Conflict
表征 LINE-1 逆转录转座-复制冲突
  • 批准号:
    10215445
  • 财政年份:
    2020
  • 资助金额:
    $ 39.68万
  • 项目类别:
Characterizing the LINE-1 Retrotransposition-Replication Conflict
表征 LINE-1 逆转录转座-复制冲突
  • 批准号:
    10440427
  • 财政年份:
    2020
  • 资助金额:
    $ 39.68万
  • 项目类别:
Expression and Impact of Interspersed Repeats
散布重复序列的表达和影响
  • 批准号:
    9983116
  • 财政年份:
    2019
  • 资助金额:
    $ 39.68万
  • 项目类别:
Expression and Impact of Interspersed Repeats
散布重复序列的表达和影响
  • 批准号:
    9816738
  • 财政年份:
    2019
  • 资助金额:
    $ 39.68万
  • 项目类别:
Expression and Impact of Interspersed Repeats
散布重复序列的表达和影响
  • 批准号:
    10409704
  • 财政年份:
    2019
  • 资助金额:
    $ 39.68万
  • 项目类别:
Exonizaton of Alu Insertion Polymorphisms
Alu 插入多态性的外显子化
  • 批准号:
    10227617
  • 财政年份:
    2017
  • 资助金额:
    $ 39.68万
  • 项目类别:
Exonizaton of Alu Insertion Polymorphisms
Alu 插入多态性的外显子化
  • 批准号:
    9444067
  • 财政年份:
    2017
  • 资助金额:
    $ 39.68万
  • 项目类别:
Opportunities for Pathology Trainees in Cancer Research
癌症研究病理学实习生的机会
  • 批准号:
    9006475
  • 财政年份:
    2015
  • 资助金额:
    $ 39.68万
  • 项目类别:
Mouse Models of Functional Insertion Polymorphisms
功能插入多态性的小鼠模型
  • 批准号:
    8423827
  • 财政年份:
    2013
  • 资助金额:
    $ 39.68万
  • 项目类别:
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