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ERC

AAMDDR — Result In Brief

Project ID: 206281
Funded under: FP7-IDEAS-ERC
Country: United Kingdom

Cell cycle and DNA damage response cross paths

The integrity of chromosomal DNA is under constant attack. Damage from internal chemicals such as free radicals and UV light from outside wreak havoc in the genetic code.
Cell cycle and DNA damage response cross paths
DNA damage initiates a multi-faceted response that delays cell cycle progression and promotes DNA repair. Failure to repair the mutated DNA can be serious and is the basis of many cancers. Human cancer-prone syndromes include ataxia telangiectasia (A-T), the A-T like disorder (ATLD) and the Seckel syndrome. These are a result of defects in specific genes of the DNA damage response such as ataxia-telangiectasia mutated (ATM) and ataxia telangiectasia and Rad3-related protein (ATR) respectively.

The EU-funded AAMDDR (DNA damage response and genome stability: The role of ATM, ATR and the Mre11 complex) project developed a novel in vitro cell-free system from Xenopus laevis egg extract to study different pathways in the DNA damage response in vertebrates.

Investigating the damage response at chromosome breaks, the team identified new mechanisms and ascertained that the damage response controls nucleotide metabolism. Screening for ATM and ATR, they identified centrosomal protein 63kDa (CEP63) as a new ATM and ATR target. The scientists also characterised Geminin coiled-coil domain-containing protein 1 (GEMC1), a novel factor involved in the initiation of DNA replication in vertebrate cells.

Functions of these genes revolve around the normal cell cycle in the wake of DNA damage. Moreover, CEP63 is required for spindle assembly mediated by the centrosome, the apparatus responsible for cell division.

The newly discovered genes are found exclusively in vertebrates and could be ideal targets for regulation of cell cycle progression that is mediated by DNA damage. Applications could involve a range of cancers and genetic disorders where these genes play a significant role.

Related information

Keywords

Cell cycle, DNA damage response, ataxia telangiectasia, Seckel Syndrome, CEP63, GEMC1
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