Cooperation of the ATM and Fanconi Anemia/BRCA Pathways in Double-Strand Break End Resection.

Clicks: 265
ID: 98373
2020
Article Quality & Performance Metrics
Overall Quality
Not rated
Combines reader engagement with the AI quality analysis. This article has not been analysed, so there is no overall score — reader engagement is measured and shown alongside.
AI Quality Assessment
Not analyzed
Readership in this journal
Emerging

Ranked #28 of 65 articles by views in Cell reports

Most read Least read

Bar heights use a square-root scale.

Mint this article as an NFT
Not yet minted

Create a permanent, verifiable on-chain record of this article on the Scimatic Network. The NFT is held in your Journament account, and you can withdraw it to your own wallet at any time.

5 SUSD one-off · no wallet required
Sign in to mint
Abstract
Cells deficient in ataxia telangiectasia mutated (ATM) are hypersensitive to ionizing radiation and other anti-cancer agents that induce double-strand DNA breaks. ATM inhibitors may therefore sensitize cancer cells to these agents. Some cancers may also have underlying genetic defects predisposing them to an ATM inhibitor monotherapy response. We have conducted a genome-wide CRISPR screen to identify genetic vulnerabilities that sensitize lung cancer cells to ATM inhibitors. Knockout of genes in the Fanconi anemia (FA)/BRCA pathway results in hypersensitivity to the ATM inhibitor M3541. Knockdown of either an FA gene or of ATM results in reduced double-strand break end resection, enhanced non-homologous end joining (NHEJ) repair, and decreased homologous recombination repair. Knockout of both the FA/BRCA pathway and ATM strongly inhibits end resection and generates toxic levels of NHEJ, thereby elucidating a mechanism of cellular death by synthetic lethality. ATM inhibitors may therefore be useful for the treatment of tumors with a defective FA/BRCA pathway.
Reference Key
cai2020cooperationcell Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Cai, Mu-Yan;Dunn, Connor E;Chen, Wenxu;Kochupurakkal, Bose S;Nguyen, Huy;Moreau, Lisa A;Shapiro, Geoffrey I;Parmar, Kalindi;Kozono, David;D'Andrea, Alan D;
Journal Cell reports
Year 2020
DOI
S2211-1247(20)30077-2
URL
Keywords
atm inhibitor crispr sgrna screening fanconi anemia pathway nhej end resection

Citations

No citations found. To add a citation, contact the admin at info@scimatic.org

Comments

No comments yet. Be the first to comment on this article.