How strand exchange protein function benefits from ATP hydrolysis

Reitz, Diedre; Chan, Yuen‐Ling; Bishop, Douglas K.

doi:10.1016/j.gde.2021.06.016

Cited by 14 publications

(11 citation statements)

References 73 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The most straightforward interpretation is that the translocase activity of RAD54 proteins is responsible for removing recombinases from dsDNA. Such unproductive association of RAD51 or DMC1 with unbroken DNA has been proposed to reflect a relatively weak preference for ssDNA over dsDNA compared to bacterial RecA recombinases (Reitz et al, 2021). Thus, our observation that C. elegans RAD-51 exhibits a similar propensity for promiscuous association with unbroken DNA that is antagonized by RAD-54.B implies that this property is a conserved aspect of eukaryotic recombinases.…”

Section: Discussionmentioning

confidence: 99%

Disparate roles forC. elegansDNA translocase paralogs RAD-54.L and RAD-54.B in meiotic prophase germ cells

Yamaya

Wang

Memar

et al. 2022

Preprint

View full text Add to dashboard Cite

RAD54 family DNA translocases partner with RAD51 recombinases to ensure stable genome inheritance, exhibiting biochemical activities both in promoting recombinase removal and in stabilizing recombinase association with DNA. Understanding how such disparate activities of RAD54 paralogs align with their biological roles is an ongoing challenge. Here we investigate the in vivo functions of C. elegans RAD54 paralogs RAD-54.L and RAD-54.B during meiotic prophase, revealing distinct contributions to the dynamics of RAD-51 association with DNA and to the progression of meiotic double-strand break repair (DSBR). While RAD-54.L is essential for RAD-51 removal from meiotic DSBR sites to enable recombination progression, RAD-54.B is largely dispensable for meiotic DSBR. However, RAD-54.B is required to prevent hyperaccumulation of RAD-51 on unbroken DNA during a key meiotic sub-stage when protein kinase CHK-2 is active. Moreover, DSB-independent hyperaccumulation of RAD-51 foci in the absence of RAD-54.B is RAD-54.L-dependent, revealing a hidden activity of RAD-54.L in promoting promiscuous RAD-51 association that is antagonized by RAD-54.B. We propose a model wherein a division of labor among RAD-54 paralogs allows germ cells to ramp up their capacity for efficient homologous recombination that is crucial to successful meiosis while counteracting potentially deleterious effects of unproductive RAD-51 association with unbroken DNA.

show abstract

Section: Discussionmentioning

confidence: 99%

Disparate roles forC. elegansDNA translocase paralogs RAD-54.L and RAD-54.B in meiotic prophase germ cells

Yamaya

Wang

Memar

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…It is worth noting that in the absence of RPA, we found that human RAD51 similarly binds to ssDNA or dsDNA (Supplementary Figure S3 A), in contrast to Saccharomyces cerevisiae’s Rad51 or Escherichia coli’s RecA recombinases, which exhibit a preferencial affinity for ssDNA. This specific property of hRAD51 raises the question of whether there is a transitory binding of RAD51 to dsDNA that should be negatively regulated, as observed in some contexts in vivo [65].…”

Section: Resultsmentioning

confidence: 99%

“…However RAD51 was shown to display faster association on ssDNA in correlation with higher ssDNA flexibility [85,86] but slower dissociation from dsDNA, the RAD51-dsDNA filament being stable once formed [87]. It has been proposed that The presence of RAD51 on dsDNA has been evidenced in vivo in certain contexts, especially in the absence of RAD54-like proteins that desassemble toxic dsDNA-bound RAD51 complexes and prevent accumulation of nonrepair-associated RAD51 foci, pointing here again to the cooperation of important factor in the regulation RAD51 [65,[88][89][90]. in spite of the fact that only filaments assembled on ssDNA are functional for homology search and strand exchange, one could still imagine that the transient and ephemeral polymerization of RAD51 on dsDNA would play a role, especially in the remodeling of certain DNA-protein complexes.…”

Section: Particular Properties Of Human Rad51 Nucleofilamentsmentioning

confidence: 99%

Human RAD52 stimulates the RAD51-mediated homology search

Muhammad

Peterlini

Guirouilh-Barbat

et al. 2022

Preprint

View full text Add to dashboard Cite

Homologous recombination (HR) is a DNA repair mechanism of double strand breaks and blocked replication forks that involves a process of homology search and homologous pairing leading to the formation of synaptic intermediates whose architecture and dynamics are tightly regulated to ensure genome integrity. In this mechanism, RAD51 recombinase plays a central role and is supported by many partner including BRCA2 and RAD52. If the mediator function of BRCA2 to load RAD51 on RPA-covered ssDNA is well established, the role of RAD52 in HR, more precisely its interplay with BRCA2 is still far from understood. We have used Transmission Electron Microscopy combined with biochemistry to characterize the sequential participation of RPA, RAD52 and BRCA2 in the assembly of the RAD51 filament, its architecture and its activity. Despite our results confirm that RAD52 lacks a mediator activity, we observed that RAD52 can tightly bind to RPA-coated ssDNA, inhibit the mediator role of BRCA2 and form shorter RAD52- and RAD51-containing mixed filaments that are more efficient in subsequent homology search and formation of synaptic complexes and D-loops, resulting in more frequent multi-invasions as well. Through the characterization of the behavior of RAD52 and BRCA2, these results provide new molecular insights on the formation and regulation of presynaptic and synaptic intermediates during human HR.

show abstract

“…Accordingly, the depletion of DSS1 in human cells disables HR repair (Kristensen et al, 2010). BRCA2 also prevents the binding of RAD51 to dsDNA (Carreira et al, 2009;Jensen et al, 2010), a binding that is inhibitory for the DNA strand exchange (reviewed in Reitz et al, 2021). Human BRCA2 protein diffuses in the cell within oligomeric complexes (Reuter et al, 2014;Paul et al, 2021).…”

Section: Brca2mentioning

confidence: 99%

Repair of DNA double-strand breaks in plant meiosis: role of eukaryotic RecA recombinases and their modulators

2022

View full text Add to dashboard Cite

Homologous recombination (HR) during meiosis is crucial for the DNA double-strand breaks (DSBs) repair that promotes the balanced segregation of homologous chromosomes and enhances genetic variation. In most eukaryotes, two recombinases RAD51 and DMC1 form nucleoprotein filaments on single-stranded DNA generated at DSB sites and play a central role in the meiotic DSB repair and genome stability. These nucleoprotein filaments perform homology search and DNA strand exchange to initiate repair using homologous template-directed sequences located elsewhere in the genome. Multiple factors can regulate the assembly, stability, and disassembly of RAD51 and DMC1 nucleoprotein filaments. In this review, we summarize the current understanding of the meiotic functions of RAD51 and DMC1 and the role of their positive and negative modulators. We discuss the current models and regulators of homology searches and strand exchange conserved during plant meiosis. Manipulation of these repair factors during plant meiosis also holds a great potential to accelerate plant breeding for crop improvements and productivity.

show abstract

How strand exchange protein function benefits from ATP hydrolysis

Cited by 14 publications

References 73 publications

Disparate roles forC. elegansDNA translocase paralogs RAD-54.L and RAD-54.B in meiotic prophase germ cells

Disparate roles forC. elegansDNA translocase paralogs RAD-54.L and RAD-54.B in meiotic prophase germ cells

Human RAD52 stimulates the RAD51-mediated homology search

Repair of DNA double-strand breaks in plant meiosis: role of eukaryotic RecA recombinases and their modulators

Contact Info

Product

Resources

About