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ATR and ATM Loss-of-Function
Mechanisms to maintain genomic integrity are essential for cells to remain viable. Not surprisingly, disruption of key DNA damage response pathway factors, such as ataxia telangiectasia-mutated (ATM)/ataxia telangiectasia and RAD3-related (ATR) results in loss of genomic integrity. Here, a synthetic lethal siRNA-screening approach not only confirmed ATM but identified additional replication checkpoint proteins, when ablated, enhanced ATR inhibitor (ATRi) response in a high-content -H2AX assay. Cancers with inactivating ATM mutations exhibit impaired DNA double-stranded break (DSB) repair and rely on compensatory repair pat...
Source: Molecular Cancer Research - January 15, 2015 Category: Cancer & Oncology Authors: Menezes, D. L., Holt, J., Tang, Y., Feng, J., Barsanti, P., Pan, Y., Ghoddusi, M., Zhang, W., Thomas, G., Holash, J., Lees, E., Taricani, L. Tags: DNA Damage and Repair Source Type: research