Inhibition of Polo-like kinase 1 during the DNA damage response is mediated through loss of Aurora A recruitment by Bora.

When cells in G2 phase are challenged with DNA damage, several key mitotic regulators such as Cdk1/Cyclin B, Aurora A and Plk1 are inhibited to prevent entry into mitosis. Here we have studied how inhibition of Plk1 is established after DNA damage. Using a Förster resonance energy transfer (FRET)-based biosensor for Plk1 activity, we show that inhibition of Plk1 after DNA damage occurs with relatively slow kinetics and is entirely dependent on loss of Plk1-T210 phosphorylation. As T210 is phosphorylated by the kinase Aurora A in conjunction with its co-factor Bora, we investigated how they are affected by DNA damage. Interestingly, we find that the interaction between Bora and Plk1 remains intact during the early phases of the DNA damage response (DDR), whereas Plk1 activity is already inhibited at this stage. Expression of an Aurora A mutant that is refractory to inhibition by the DDR failed to prevent inhibition of Plk1 and loss of T210 phosphorylation, suggesting that inhibition of Plk1 may be established by perturbing recruitment of Aurora A by Bora. Indeed, expression of a fusion in which Aurora A was directly coupled to Bora prevented DNA damage-induced inhibition of Plk1 activity, as well as inhibition of T210 phosphorylation. Taken together, these data demonstrate that DNA damage affects the function of Aurora A at multiple levels: both by direct inhibition of Aurora A activity, as well as by perturbing the interaction with its co-activator Bora. We propose that the DDR targets recruitment of Aurora A to the Plk1/Bora complex to prevent activation of Plk1 during DNA damage in G2.

Psoriasis and arthritis. I. A population study.

In a population survey of 3659 persons aged 20 years or older, no association was found between psoriasis and rheumatoid arthritis. Inflammatory, degenerative and soft tissue rheumatic diseases occurred in 59% of the psoriatics and 46% of the controls. However, the mean number of rheumatological diagnoses in the psoriatics was 1.1 and in the controls 1.3. Features of psoriasis were found in 41 individuals (1.1%). Features of inflammatory arthritis (RA + past-polyarthritis) were established in 5% and 2.2% of the psoriatics and the controls respectively, but this difference is not significant. Because patients with psoriasis have complaints associated with the locomotor system more frequently than non-psoriatic people, it seems likely that the referral rate of the former to special clinics is higher.