G2/M checkpoint activation after DNA damage results in G2/M cell cycle arrest that allows time for DNA repair before the entry of cells into mitosis. Activation of G2/M checkpoint involves a series of signaling events, which include activation of ataxia telangiectecia-mutated and Rad3-related (ATR) and Chk1 kinases and inhibition of Cdc2/Cyclin B activity. Studies presented in this report show that serine (Ser)/threonine (Thr) protein phosphatase 2A (PP2A) has an important role in G2/M checkpoint activation in response to γ-irradiation (IR) exposure. Using PP2A inhibitors, as well as siRNA targeting various forms of Ser/Thr protein phosphatases, results presented in this report show that specific PP2A inhibition abrogates IR-induced activation of ATR and Chk1 kinases, as well as phosphorylation of Cdc2-Tyr15, and attenuates IR-induced G2/M arrest. These results suggest an important regulation of PP2A on IR-induced G2/M checkpoint signaling response.

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Competing hypotheses for the development of midface hypoplasia in patients with cleft lip and palate include both theories of an intrinsic restricted growth potential of the midface and extrinsic surgical disruption of maxillary growth centers and scar growth restriction secondary to palatoplasty. The following meta-analysis aims to better understand the intrinsic growth potential of the midface in a patient with cleft lip and palate unaffected by surgical correction. A systematic review of studies reporting cephalometric measurements in patients with unoperated and operated unilateral cleft lip and palate (UCLP), bilateral cleft lip and palate (BCLP), and isolated cleft palate (iCP) abstracted SNA and ANB angles, age at cephalometric analysis, syndromic diagnosis, and patient demographics. Age and Regionmatched controls without cleft palate were used for comparison. SNA angle for unoperated UCLP (84.5 AE 4.08), BCLP (85.3 AE 2.88), and ICP (79.2 AE 4.28) were statistically different than controls (82.4 AE 3.58), (all P 0.001). SNA angles for operated UCLP (76.2 AE 4.28), BCLP (79.8 AE 3.68), and ICP (79.0 AE 4.38) groups were statistically smaller than controls (all P 0.001). SNA angle in unoperated ICP (n ¼ 143) was equivalent to operated ICP patients (79.2 AE 4.28 versus 79.0 AE 4.38 P ¼ 0.78). No unoperated group mean SNA met criteria for midface hypoplasia (SNA < 80). Unoperated UCLP/BLCP exhibit a more robust growth potential of the maxilla, whereas operated patients demonstrate stunted growth compared to normal phenotype. Unoperated ICP demonstrates restricted growth in both operated and unoperated patients. As such, patients with UCLP/BCLP differ from patients with ICP and the factors affecting midface growth may differ. Level of Evidence: IV