Sunday, October 05, 2008

Stability Enables DNA Repair

Control of DNA polymerase stability by phosphorylation and ubiquitination during the cell cycle (EMBO reports 9, 10, 1027–1033 2008; doi:10.1038/embor.2008.148) by Ursula Wimmer, Elena Ferrari, Peter Hunziker and Ulrich Hübscher, indicates that a DNA repair enzyme, dubbed DNA polymerase (Pol) (Greek letter lamda), is stabilized during the cell cycle through phophorylation. It is speculated that this enables the enzyme to repair damaged DNA during and after a phase of the cell cycle known as S. From the abstract (Greek letter lamda substituting for the actual symbol):


DNA polymerase (Pol) (Greek letter lamda) is a DNA repair enzyme involved in base excision repair, non-homologous end joining and translesion synthesis. Recently, we identified Pol as an interaction partner of cyclin-dependent kinase 2 (CDK2) that is central to the cell cycle G1/S transition and S-phase progression. This interaction leads to in vitro phosphorylation of Pol (Greek letter lamda), and its in vivo phosphorylation pattern during cell cycle progression mimics the modulation of CDK2/cyclin A. Here, we identify several phosphorylation sites of Pol (Greek letter lamda). Experiments with phosphorylation-defective mutants suggest that phosphorylation of Thr 553 is important for maintaining Pol (Greek letter lamda) stability, as it is targeted to the proteasomal degradation pathway through ubiquitination unless this residue is phosphorylated. In particular, Pol (Greek letter lamda) is stabilized during cell cycle progression in the late S and G2 phases. This most likely allows Pol (Greek letter lamda) to correctly conduct repair of damaged DNA during and after S phase.

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