Mad2l2 role in the maintenance of pluripotency

Open chromatin is induced locally during the repair of DNA double strand breaks, when a cascade of protein recruitments and modifications is triggered. This "ATM cascade" includes components like the Mrn complex, ATM kinase, phosphorylated histon variant ?H2AX, MDC1, E3 ligases RNF 8 and RNF8, 53BP1, and Rif1. Recent investigations have shown that also the Mad2l2 protein is a downstream effector of the ATM cascade during DNA repair. It was first described as an accessory subunit during translesion DNA repair, and more recently as a key factor inhibiting the resection of DNA 5`ends, thus promoting non-homologous end joining, and repressing homologous recombination.Naive embryonic stem cells (ESCs) have a globally open chromatin. A preliminary study from this laboratory has demonstrated that ESCs require the presence of the Mad2l2 protein for the maintenance of their transcriptional and epigenetic profiles, and thus for the stability of pluripotency (Pirouz et al., Cell Cycle 14, 1596, 2015). The aim of the present study was to correlate Mad2l2 with the ATM cascade and the chromatin status in ESCs.

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