A whole genome RNAi screen identifies replication stress response genes

Gina Kavanaugh, Fei Ye, Kareem N. Mohni, Jessica W. Luzwick, Gloria Glick, David Cortez

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Proper DNA replication is critical to maintain genome stability. When the DNA replication machinery encounters obstacles to replication, replication forks stall and the replication stress response is activated. This response includes activation of cell cycle checkpoints, stabilization of the replication fork, and DNA damage repair and tolerance mechanisms. Defects in the replication stress response can result in alterations to the DNA sequence causing changes in protein function and expression, ultimately leading to disease states such as cancer. To identify additional genes that control the replication stress response, we performed a three-parameter, high content, whole genome siRNA screen measuring DNA replication before and after a challenge with replication stress as well as a marker of checkpoint kinase signalling. We identified over 200 replication stress response genes and subsequently analyzed how they influence cellular viability in response to replication stress. These data will serve as a useful resource for understanding the replication stress response.

Original languageEnglish (US)
Pages (from-to)55-62
Number of pages8
JournalDNA Repair
Volume35
DOIs
StatePublished - Nov 1 2015

Keywords

  • ATR
  • Camptothecin
  • Checkpoint
  • DNA damage
  • Gemcitabine
  • Hydroxyurea
  • PARP inhibitor
  • RNAi screen
  • Replication stress

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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