Yates, L. | bioRxiv Science

bioRxiv2024

Molecular basis of FIGNL1 in dissociating RAD51 from DNA and chromatin

Maintaining genome integrity is an essential and challenging process. RAD51 recombinase, the central player of several crucial processes in repairing and protecting genome integrity, forms filaments on DNA. RAD51 filaments are tightly regulated. One of these regulators is FIGNL1, that prevents persistent RAD51 foci post-damage and genotoxic chromatin association in cells. The cryogenic electron microscopy structure of FIGNL1 in complex with RAD51 reveals that the FIGNL1 forms a non-planar hexamer and RAD51 N-terminus is enclosed in the FIGNL1 hexamer pore. Mutations in pore loop or catalytic residues of FIGNL1 render it defective in filament disassembly and are lethal in mouse embryonic stem cells. Our study reveals a unique mechanism for removing RAD51 from DNA and provides the molecular basis for FIGNL1 in maintaining genome stability.

biochemistry↗

bioRxiv2023

Phylogenetically conservative trait correlation: quantification and interpretation

O_LICorrelation across species between two quantitative traits, or between a trait and a habitat property, can suggest that a trait value is effective in sustaining populations in some contexts but not others. It is widely held that such correlations should be controlled for phylogeny, via phylogenetically independent contrasts PICs or phylogenetic generalised least squares PGLS. C_LIO_LITwo weaknesses of this idea are discussed. First, the phylogenetically conservative share of the correlation ought not to be excluded from consideration as potentially ecologically functional. Second, PGLS does not yield a complete or accurate breakdown of A-B covariation, because it corresponds to a generating model where B predicts variation in A but not the reverse. C_LIO_LIMulti-response mixed models using phylogenetic covariance matrices can quantify conservative trait correlation CTC, a share of covariation between traits A and B that is phylogenetically conservative. Because the evidence is from correlative data, it is not possible to split CTC into causation by phylogenetic history versus causation by continuing reciprocal selection between A and B. Moreover, it is quite likely biologically that the two influences have acted in concert, through phylogenetic niche conservatism. C_LIO_LISynthesis: The CTC concept treats phylogenetic conservatism as a conjoint interpretation alongside ongoing influence of other traits. CTC can be quantified via multi-response phylogenetic mixed models. C_LI

ecology↗