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DDB_G0293866 has both N and C-terminal domains similar to aprataxin and contains a poly-ADP ribose binding domain. Aprataxin is suspected to play a role in several different DNA repair pathways, specifically by resolving abortive ligation intermediates [see Ahe et. al, Nature 443, 713-6 (2006); Rass et al., JBC 282, 9469-9474 (2007).]

DDB_GO293866 is 5-fold overexpressed in a Dicty strain in which the retinoblastoma-like gene rblA has been disrupted (Doquang et al, in preparation). Genes whose products are involved in replication-coupled DNA repair are generally overexpressed 3 to 6-fold in this strain, while genes in replication-independent repair pathways are overexpressed by smaller factors if at all. In mammalian cells, aprataxin interacts with XRCC1 and Ligase3, which are involved in (replication-independent) excision repair. The corresponding Dictyostelium genes are overexpressed less than twofold in the rblA-disruptant.

When "reverse blasted", DDB_GO293866 is only the third hit of aprataxin in the Dicty genome. Neither the first- nor the second-hit genes are substantially upregulated in the rblA-disruptant. Although there is only one aprataxin in the mammalian genome, there are many isoforms, encoded by transcript variants. In Dictyostelium it seems possible that there are several genes which are specialized for action in different repair pathways. If this is true, it is likely that DDB_GO293866 is involved in a replication-coupled repair process. Possible interaction partners in such a pathway include the products of PNKP, xrcc4, lig4, and adprt1B, all of which are overexpressed by similar factors.

Harry MacWilliams, September 2009

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