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DNA Repair (Amst). 2009 Sep 2;8(9):1025-37. doi: 10.1016/j.dnarep.2009.04.015. Epub 2009 May 23.

Studying the DNA damage response using in vitro model systems.

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Genome Stability Unit, London Research Institute, Clare Hall Laboratories, South Mimms, Herts EN6 3LD, United Kingdom.


Exogenous and endogenous insults continuously damage DNA. DNA damage must be detected in order to prevent loss of vital genetic information. Cells respond to DNA damage by activating checkpoint pathways that delay the progression through the cell cycle, promote DNA repair or induce cell death. A regulatory network of proteins has been identified that participate in DNA damage checkpoint pathways. Central to this network are ATM, ATR and the Mre11/Rad50/Nbs1 (MRN) complex. Detailed biochemical analysis of ATM, ATR and the MRN dependent DNA damage responses has taken advantage of several in vitro model systems to understand the detailed mechanisms underlying their function. Here we describe some recent findings obtained analysing these pathways using in vitro model systems. In particular we focus on the studies performed in the Xenopus laevis egg cell free extract, which recapitulates the DNA damage response in the context of the cell cycle.

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