Antibodies Targeting S-Phase Checkpoint Signalling Pathways

Fri, 02/05/2010 - 09:14

Research into checkpoint signalling (CPS) forms a major part of IHC research. CPS regulates DNA repair mechanisms, apoptosis and cell cycle progression. Antibody research into checkpoint proteins has also shown they play an essential role in tumour development. ATM and ATR are two important checkpoint mediators which are well reported in cancer studies.

Cellular checkpoints are signal transduction pathways which interact with many other mechanisms, such as that governing growth factor availability. We at Novus Biologicals have a large number of CPS immunoglobulins on our antibody database.

The S-phase checkpoint is involved with DNA repair and cell-cycle progression. It is known to react to DNA damage by reducing the rate of synthesis. Although it is still the least understood of the cellular checkpoints, recent studies on infrared-induced S-phase checkpoint activation have thrown valuable insight into its role in cancer development. Ataxia Telangiectasia (AT) and Nijmegen Breakage Syndrome (NBS) are genetic diseases that increase the risk of tumour cell development. Cells from NBS and AT patients showed the rate of DNA synthesis did not decrease following exposure to infrared radiation. This is known as radio-resistant DNA synthesis (RDS).

Studies show that IR damage activates the checkpoint via 2 parallel branches, both regulated by ATM. In the first, ATM is induced to phosphorylate the Chk2 kinase, which leads to degradation of Cdc25A phosphatise. The net result is that the Cdk2/Cyclin E and Cdk2/Cyclin A complexes are prevented from becoming active and inhibiting DNA synthesis.

The second branch is independent of Chk2. IR damage triggers ATM to phosphorylate a number of substrates including NBS1, BRCA1 and SMC. Mutation or disruption of this function results in reduced S-phase checkpoint activation.

Phosphorylated and conjugated antibodies specific to these proteins are used in signalling studies to further our understanding of the role checkpoints play in cancer.


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