Homologous recombination, cancer and the ‘RAD51 paradox’

Genetic instability is a hallmark of cancer cells. Homologous recombination (HR) plays key roles in genome stability and variability due to its roles in DNA double-strand break and interstrand crosslink repair, and in the protection and resumption of arrested replication forks. HR deficiency leads to genetic instability, and, as expected, many HR genes are downregulated in cancer cells. The link between HR deficiency and cancer predisposition is exemplified by familial breast and ovarian cancers and by some subgroups of Fanconi anaemia syndromes. Surprisingly, although RAD51 plays a pivotal role in HR, i.e., homology search and in strand exchange with a homologous DNA partner, almost no inactivating mutations of RAD51 have been associated with cancer predisposition; on the contrary, overexpression of RAD51 is associated with a poor prognosis in different types of tumours. Taken together, these data highlight the fact that RAD51 differs from its HR partners with regard to cancer susceptibility and expose what we call the ‘RAD51 paradox’. Here, we catalogue the dysregulations of HR genes in human pathologies, including cancer and Fanconi anaemia or congenital mirror movement syndromes, and we discuss the RAD51 paradox.

Crossed Czerny–Turner Spectrometer with Extended Spectrum Using Movable Planar Mirrors

This study reports a crossed Czerny–Turner spectrometer with multiple mirrors to extend the inspected spectrum. A design example with two movable mirrors and a stationary planar mirror is experimentally demonstrated to offer two additional spectral bands, thereby leading to thrice the spectral range of the original Czerny–Turner spectrometer. The results indicate that the configurations to measure the three bands have almost identical parameters. The moving direction of the planar mirror and the plane of incidence are orthogonal; thus, the influence of mirror movement on the repeatability of the spectrum is minimized. In addition to the merits of cost-effectiveness and rapid inspection, the reported mechanism of mirror movement is applied to general spectrometers to extend the spectral coverage without sacrificing the resolution.

The Relationship Between Hand Function and Overlapping Motor Representations of the Hands in the Contralesional Hemisphere in Unilateral Spastic Cerebral Palsy

Background. In many children with unilateral spastic cerebral palsy (USCP), the corticospinal tract to the affected hand atypically originates in the hemisphere ipsilateral to the affected hand. Such ipsilateral connectivity is on average a predictor of poor hand function. However, there is high variability in hand function in these children, which might be explained by the complexity of motor representations of both hands in the contralesional hemisphere. Objective. To measure the link between hand function and the size and excitability of motor representations of both hands, and their overlap, in the contralesional hemisphere of children with USCP. Methods. We used single-pulse transcranial magnetic stimulation to measure the size and excitability of motor representations of both hands, and their overlap, in the contralesional hemisphere of 50 children with USCP. We correlated these measures with manual dexterity of the affected hand, bimanual performance, and mirror movement strength. Results. The main and novel findings were (1) the large overlap in contralesional motor representations of the 2 hands and (2) the moderate positive associations of the size and excitability of such shared-site representations with hand function. Such functional associations were not present for overall size and excitability of representations of the affected hand. Conclusions. Greater relative overlap of the affected hand representation with the less-affected hand representation within the contralesional hemisphere was associated with better hand function. This association suggests that overlapping representations might be adaptively “yoked,” such that cortical control of the child’s less-affected hand supports that of the affected hand.