Multi‐Invasion‐Induced Rearrangements as a Pathway for Physiological and Pathological Recombination

Heyer, Wolf‐Dietrich

doi:10.1002/bies.201700249

Cited by 28 publications

(31 citation statements)

References 84 publications

(129 reference statements)

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“…Our analysis also suggests the occurrence of multi-invasion repair (MIR), a subtype of HR, and micro-homology-mediated BIR (MMBIR), both of which can be favored for the repair of repeat sequences 6, 51 . According to the MIR pathway, a single broken end might enter multiple target DNA molecules based on homology 52, 53 . The DNA breaks in our experiments were made in the Tcn2 element, which is present in multiple copies across centromeres; thus, it is possible that some of the ends might have been repaired via MIR.…”

Section: Discussionmentioning

confidence: 99%

Centromere scission drives chromosome shuffling and reproductive isolation

Yadav

Sun

Coelho

et al. 2019

Preprint

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AbstractA fundamental characteristic of eukaryotic organisms is the generation of genetic variation via sexual reproduction. Conversely, significant large-scale genome structure variations could hamper sexual reproduction, causing reproductive isolation and promote speciation. The underlying processes behind large-scale genome rearrangements are not well understood and include chromosome translocations involving centromeres. Recent genomic studies in the Cryptococcus species complex revealed that chromosome translocations generated via centromere recombination have reshaped the genomes of different species. In this study, multiple DNA double-strand breaks (DSBs) were generated via the CRISPR/Cas9 system at centromere-specific retrotransposons in the human fungal pathogen Cryptococcus neoformans. The resulting DSBs were repaired in a complex manner, leading to the formation of multiple inter-chromosomal rearrangements and new telomeres, similar to chromothripsis-like events. The newly generated strains harboring chromosome translocations exhibited normal vegetative growth but failed to undergo successful sexual reproduction with the parental wild-type strain. One of these strains failed to produce any spores, while another produced ∼3% viable progeny. The germinated progeny exhibited aneuploidy for multiple chromosomes and showed improved fertility with both parents. All chromosome translocation events were accompanied without any detectable change in gene sequences and thus, suggest that chromosomal translocations alone may play an underappreciated role in the onset of reproductive isolation and speciation.

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Section: Discussionmentioning

confidence: 99%

Centromere scission drives chromosome shuffling and reproductive isolation

Yadav

Sun

Coelho

et al. 2019

Preprint

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“…The D-loop disruption mechanism is enhanced by mismatch repair proteins at mismatched hDNA in a process termed heteroduplex rejection (Chakraborty et al, 2016). Furthermore, the dynamic nature of D-loops endowed by these enzymes also prevents concomitant invasions, either of both broken ends in the same donor molecule leading to double Holliday Junctions (dHJ) (Wright et al, 2018;, or of a single end into two different donors leading to multi-invasions (MI) (Piazza & Heyer, 2018;Piazza et al, 2017), thus inhibiting downstream covalent alterations of the donors mediated by structure-selective endonucleases (SSEs). Indeed, both crossovers and MI-induced rearrangements increase in mph1, sgs1-top3-rmi1, and srs2 mutants (Ira et al, 2003;Piazza et al, 2017;Prakash et al, 2009aPrakash et al, , 2009b.…”

Section: Introductionmentioning

confidence: 99%

Rdh54/Tid1 Inhibits Rad51-Rad54-Mediated D-loop Formation and Limits D-loop Length

Shah

Hartono

Som

et al. 2020

Preprint

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Displacement loops (D-loops) are intermediates formed during homologous recombination that play a pivotal role in the fidelity of repair. Rdh54 (a.k.a. Tid1), a Rad54 paralog in Saccharomyces cerevisiae, is well-known for its role with Dmc1 recombinase during meiotic recombination. Yet contrary to Dmc1, Rdh54 is also present in somatic cells where its function is less understood.While Rdh54 enhances the Rad51 DNA strand invasion activity in vitro, it is unclear how it interplays with Rad54-mediated invasions. Here, we show that Rdh54 inhibits D-loop formation by Rad51 and Rad54 in an ATPase-independent manner. Using a novel D-loop Mapping Assay, we further demonstrate that Rdh54 uniquely restricts the lengths of Rad54-mediated D-loops. The alterations in D-loop properties appear to be important for cell survival and mating-type switch in haploid yeast, whereas Rdh54 expression is suppressed in diploids. We propose that Rdh54 and Rad54 compete for potential binding sites within the Rad51 filament, where Rdh54 acts as a physical roadblock to Rad54's translocation activity, limiting D-loop formation and D-loop length.

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“…The eukaryotic RAD51 gene is a homologue of the RecA gene of Escherichia coli . RAD51 forms a complex with the “breast cancer susceptibility gene 2” (BRCA2) and plays a central role in the homologous recombination (HR) repair of a variety of DNA lesions such as the DNA double‐strand breaks (DSB) . Homologous recombination (HR) is catalysed by the RAD51 recombinase, which forms a nucleoprotein filament on resected single‐stranded DNA (ssDNA) at the damage site, and mediates pairing of the homologous DNA sequences and strand invasion .…”

Section: Introductionmentioning

confidence: 99%

The canine RAD51 mutation leads to the attenuation of interaction with PALB2

Uemura

Ochiai

Morimatsu

et al. 2019

Vet Comparative Oncology

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RAD51 forms a complex with BRCA2 and plays a central role in the DNA damage response pathway that is associated with homologous recombination. The structures of RAD51 and its homologues are highly conserved from prokaryotes to higher eukaryotes. Although a large number of BRCA2 mutations have been reported, there are only a few reports on the mutations of RAD51, which have been shown in humans and dogs. However, several mutations of canine RAD51 were identified from mammary gland tumour tissues in a recent study. Some of these mutations seem to have an influence on the homo-oligomerization or interaction with "Partner and localizer of BRCA2" (PALB2). In this study, we cloned the canine PALB2 homologue and investigated the effect on its interaction with the RAD51 mutants to evaluate the alteration in the function of RAD51 mutants. The A209S and T225S mutants of RAD51 show an attenuation of the interaction between RAD51 and PALB2. These results indicate that the canine RAD51 mutations can potentially alter the homologous recombination pathways in response to DNA damage in dogs. K E Y W O R D SBRCA2, cancer-associated single nucleotide polymorphisms (SNPs), DNA double-strand breaks (DSB), homologous recombination (HR), mammary gland tumour

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Multi‐Invasion‐Induced Rearrangements as a Pathway for Physiological and Pathological Recombination

Cited by 28 publications

References 84 publications

Centromere scission drives chromosome shuffling and reproductive isolation

Centromere scission drives chromosome shuffling and reproductive isolation

Rdh54/Tid1 Inhibits Rad51-Rad54-Mediated D-loop Formation and Limits D-loop Length

The canine RAD51 mutation leads to the attenuation of interaction with PALB2

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