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National Institute of Environmental Health Sciences

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Publication Detail

Title: A whole genome RNAi screen identifies replication stress response genes.

Authors: Kavanaugh, Gina; Ye, Fei; Mohni, Kareem N; Luzwick, Jessica W; Glick, Gloria; Cortez, David

Published In DNA Repair (Amst), (2015 Nov)

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.

PubMed ID: 26454783 Exiting the NIEHS site

MeSH Terms: Cell Line, Tumor; Checkpoint Kinase 1; DNA Damage*; DNA Repair; DNA Replication/genetics*; DNA, Single-Stranded/genetics; Genome, Human/genetics*; Genomic Instability; Genomics; Humans; Microscopy, Fluorescence; Protein Kinases/metabolism; RNA Interference*; RNA, Small Interfering/genetics*

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