Reed starts each class by sharing this story, and teaching students how to mitigate pain and prevent injuries of their own. They urge students to spend a few minutes a day going through self-massaging techniques. Reed demonstrates how to massage their diaphragm muscle tissue near the edge of the binder and how to roll a tennis ball against their trapezius muscle using a corner of a wall. In another technique, Reed lies down on a roller and extends their arms toward the floor, opening their chest.
Cyclin A2 activates the cyclin-dependent kinases Cdk1 and Cdk2 and is expressed at elevated levels from S phase until early mitosis. We found that mutant mice that cannot elevate cyclin A2 are chromosomally unstable and tumor-prone. Underlying the chromosomal instability is a failure to up-regulate the meiotic recombination 11 (Mre11) nuclease in S phase, which leads to impaired resolution of stalled replication forks, insufficient repair of double-stranded DNA breaks, and improper segregation of sister chromosomes. Unexpectedly, cyclin A2 controlled Mre11 abundance through a C-terminal RNA binding domain that selectively and directly binds Mre11 transcripts to mediate polysome loading and translation. These data reveal cyclin A2 as a mechanistically diverse regulator of DNA replication combining multifaceted kinase-dependent functions with a kinase-independent, RNA binding–dependent role that ensures adequate repair of common replication errors.
Many biological processes involve macromolecular interactions, and knowing the binding energies of these interactions is key to a functional understanding. There are several experimental approaches to calculate binding energies in bulk solutions, but these require that the binding is at equilibrium. Camunas-Soler et al. used a fluctuation theorem for binding reactions to extract ligand binding energies directly from force experiments that probed a single binding reaction. They resolved binding energies of peptides to specific and non-specific DNA binding sites with affinities spanning six orders of magnitude.
An unexpected function of the oxidized form of nicotinamide adenine dinucleotide (NAD) could underlie some effects of aging and propensity to age-related diseases. Li et al. found that the protein DBC1 (deleted in breast cancer 1) contains a domain that specifically binds NAD . Binding of NAD inhibited the interaction of DBC1 with PARP1 [poly(adenosine diphosphate–ribose) polymerase 1], an enzyme important in DNA repair. Activity of PARP1 is inhibited by interaction with DBC1. Thus, the reduced abundance of NAD associated with aging may decrease PARP1 activity by promoting the interaction of PARP1 with DBC1.