DDB_G0274161 - dictyBase/community-annotations GitHub Wiki

DDB_G0274161 is similar to nmr1, originally identified as a Neurospora gene which binds to the transcription factor nit2, and prevents its binding to and activating genes required for nitrogen utilization. The human ortholog is "NmrA-like", known as NMRAL1 or HSCARG, and is said to monitor the ratio of NAD to NADPH, acting as a redox sensor, which moves to the nucleus when NADPH/NAD drops below a threshold value Zheng et al, PNAS 104, (2007).

DDB_G0274161 is sevenfold overexpressed in a Dicty strain in which the retinoblastoma-like gene rblA has been disrupted (Doquang et al, in preparation). Most genes with roles in S-phase or mitosis are overexpressed in this strain. It is not immediately obvious what role a redox sensor could be expected to play in cell cycle progression. However, it has been shown that activated NMRAL1/HSCARG downregulates the synthesis of nitrous oxide by associating with and inhibiting arginosuccinate synthase Zhao et al, JBC 283, (2008). Nitrous oxide is well known to destroy vitamin B12, which is involved in thymidine biosynthesis. Vitamin B12 is involved in the regeneration of folate, and folate is required as a methyl-group donor in the synthesis of thymidine from uridine.

Other genes in this pathway are in fact upregulated in the rblA disruptant; these include thymidylate synthase, which carries out the methylation of dUMP (threefold overexpressed) and DDB_G0274527, a vitamin B12 biosynthetic enzyme (also threefold). Perhaps the simplest interpretation for the overexpression of DDB_G0274161 is that Dicty NMRAL1/HSCARG is involved in the regulation of vitamin B12 levels, thus indirectly contributing to DNA replication.

Harry MacWilliams, October 2009

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