Antagonism between BRCA2 and FIGL1 regulates homologous recombination

Kumar, Rajeev; Duhamel, Marine; Coutant, Eve; Ben-Nahia, Emna; Mercier, Raphaël

doi:10.1093/nar/gkz225

Cited by 30 publications

(35 citation statements)

References 49 publications

(67 reference statements)

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“…It is possible that in human cells this interaction may be SPIDR-mediated as SPIDR also binds to FIGNL1 (45). A similar antagonistic mechanism has been reported between Arabidopsis thaliana FIGL1 and BRCA2 (51).…”

Section: Discussionsupporting

confidence: 79%

The human Shu complex functions with PDS5B and SPIDR to promote homologous recombination

Martino

Brunette

Barroso-González

et al. 2019

Nucleic Acids Research

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RAD51 plays a central role in homologous recombination during double-strand break repair and in replication fork dynamics. Misregulation of RAD51 is associated with genetic instability and cancer. RAD51 is regulated by many accessory proteins including the highly conserved Shu complex. Here, we report the function of the human Shu complex during replication to regulate RAD51 recruitment to DNA repair foci and, secondly, during replication fork restart following replication fork stalling. Deletion of the Shu complex members, SWS1 and SWSAP1, using CRISPR/Cas9, renders cells specifically sensitive to the replication fork stalling and collapse caused by methyl methanesulfonate and mitomycin C exposure, a delayed and reduced RAD51 response, and fewer sister chromatid exchanges. Our additional analysis identified SPIDR and PDS5B as novel Shu complex interacting partners and genetically function in the same pathway upon DNA damage. Collectively, our study uncovers a protein complex, which consists of SWS1, SWSAP1, SPIDR and PDS5B, involved in DNA repair and provides insight into Shu complex function and composition.

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Section: Discussionsupporting

confidence: 79%

The human Shu complex functions with PDS5B and SPIDR to promote homologous recombination

Martino

Brunette

Barroso-González

et al. 2019

Nucleic Acids Research

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“…However, when calculating the per site recombination rate to account for effective population size, KES had an average recombination rate that was an order of magnitude larger than the other populations. As demonstrated within previous studies, populations with a small effective population size may exhibit higher recombination rates associated to an increase accumulation of deleterious mutations in homogenized genomes (Keightley and Otto 2006; Kumar et al 2019; Schwarzkopf et al 2020). Because KES has had a small historical Ne (~10,000), we hypothesize that the deleterious effects of a low Ne have contributed to a increased overall recombination rates within KES; however, this hypothesis needs to be tested.…”

Section: Discussionmentioning

confidence: 51%

Evolutionary implications of recombination differences across diverging populations ofAnopheles

Nelson

Cornejo

2021

Preprint

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Recombination is one of the main evolutionary mechanisms responsible for changing the genomic architecture of populations; and in essence, it is the main mechanism by which novel combinations of alleles, haplotypes, are formed. A clear picture that has emerged across study systems is that recombination is highly variable, even among closely related species. However, it is only until very recently that we have started to understand how recombination variation between populations of the same species impact genetic diversity and divergence. Here, we used whole-genome sequence data to build fine-scale recombination maps for nine populations within two species of Anopheles, Anopheles gambiae and Anopheles coluzzii. The genome-wide recombination averages were on the same order of magnitude for all populations except one. Yet, we identified significant differences in fine-scale recombination rates among all population comparisons. We report that effective population sizes, and presence of a chromosomal inversion has major contribution to recombination rate variation along the genome and across populations. We identified over 400 highly variable recombination hotspots across all populations, where only 9.6% are shared between two or more populations. Additionally, our results are consistent with recombination hotspots contributing to both genetic diversity and absolute divergence (dxy) between populations and species of Anopheles. However, we also show that recombination has a small impact on population genetic differentiation as estimated with FST. The minimal impact that recombination has on genetic differentiation across populations represents the first empirical evidence against recent theoretical work suggesting that variation in recombination along the genome can mask or impair our ability to detect signatures of selection. Our findings add new understanding to how recombination rates vary within species, and how this major evolutionary mechanism can maintain and contribute to genetic variation and divergence within a prominent malaria vector.

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“…Each single focus found at an epifluorescence microscope is composed of several smaller foci at the STED (compare RAD51 staining in Figures 2 , 5 ). While RAD51 foci, for example, were found to be mainly circular and peak in zygotene at around 200 foci per nucleus in widefield images ( Kumar et al, 2019 ; Sims et al, 2019 ; Kurzbauer et al, 2021 ), more than 1,000 foci are found in images acquired by STED nanoscopy ( Figure 5 ). In addition, foci seem to assume different shapes over time, with few larger clusters forming in pachytene and likely representing different repair intermediates.…”

Section: From Microscopy To Nanoscopy: New Views On Meiosismentioning

confidence: 99%

From Microscopy to Nanoscopy: Defining an Arabidopsis thaliana Meiotic Atlas at the Nanometer Scale

2021

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Visualization of meiotic chromosomes and the proteins involved in meiotic recombination have become essential to study meiosis in many systems including the model plant Arabidopsis thaliana. Recent advances in super-resolution technologies changed how microscopic images are acquired and analyzed. New technologies enable observation of cells and nuclei at a nanometer scale and hold great promise to the field since they allow observing complex meiotic molecular processes with unprecedented detail. Here, we provide an overview of classical and advanced sample preparation and microscopy techniques with an updated Arabidopsis meiotic atlas based on super-resolution microscopy. We review different techniques, focusing on stimulated emission depletion (STED) nanoscopy, to offer researchers guidance for selecting the optimal protocol and equipment to address their scientific question.

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Antagonism between BRCA2 and FIGL1 regulates homologous recombination

Cited by 30 publications

References 49 publications

The human Shu complex functions with PDS5B and SPIDR to promote homologous recombination

The human Shu complex functions with PDS5B and SPIDR to promote homologous recombination

Evolutionary implications of recombination differences across diverging populations ofAnopheles

From Microscopy to Nanoscopy: Defining an Arabidopsis thaliana Meiotic Atlas at the Nanometer Scale

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