Moving forward one step back at a time: reversibility during homologous recombination

Heyer, Wolf Dietrich

doi:10.1007/s00294-019-00995-7

Cited by 42 publications

(48 citation statements)

References 69 publications

(77 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These results suggest that Rad9 promotes strand invasion and D-loop extension in BIR, through a mechanism independent of Chk1 and Rad53 signalling. Of note, previous studies show that the annealing between the two DNA strands in D-loop formation can either be promoted by a Rad51-dependent process or rejected by the Sgs1-Top3-Rmi1 complex and Mph1 4,5,[22][23][24][25] . Strikingly, the genetic deletions of the two helicases Sgs1 and Mph1 in JRL092 rad9Δ cells partially rescued cell viability ( Fig.…”

Section: Rad9 Limits Sgs1 and Mph1 To Promote D-loop Extensionmentioning

confidence: 99%

“…Of note, D-loops can be extended and processed in different ways, promoting a variety of HR subpathways, with/without crossover (CO). Moreover, nascent Dloops can be reversed by specific helicases and/or topoisomerases (Srs2, Mph1 and Sgs1-Top3-Rmi1 (STR) in yeast; BLM-TOPIIIα-RMI1/2, FANCJ, FBH1, PARI, RECQ1, RECQ5, RTEL1, FANCM, and maybe others in human), through finely regulated mechanisms that, according to recent data in yeast, also involve the Rad54-paralog Rdh54/Tid1 4,5 .…”

mentioning

confidence: 99%

See 1 more Smart Citation

Rad9/53BP1 promotes DNA repair via crossover recombination by limiting the Sgs1 and Mph1 helicases

et al. 2020

View full text Add to dashboard Cite

The DNA damage checkpoint (DDC) is often robustly activated during the homologous recombination (HR) repair of DNA double strand breaks (DSBs). DDC activation controls several HR repair factors by phosphorylation, preventing premature segregation of entangled chromosomes formed during HR repair. The DDC mediator 53BP1/Rad9 limits the nucleolytic processing (resection) of a DSB, controlling the formation of the 3′ single-stranded DNA (ssDNA) filament needed for recombination, from yeast to human. Here we show that Rad9 promotes stable annealing between the recombinogenic filament and the donor template in yeast, limiting strand rejection by the Sgs1 and Mph1 helicases. This regulation allows repair by long tract gene conversion, crossover recombination and break-induced replication (BIR), only after DDC activation. These findings shed light on how cells couple DDC with the choice and effectiveness of HR sub-pathways, with implications for genome instability and cancer.

show abstract

Section: Rad9 Limits Sgs1 and Mph1 To Promote D-loop Extensionmentioning

confidence: 99%

mentioning

confidence: 99%

Rad9/53BP1 promotes DNA repair via crossover recombination by limiting the Sgs1 and Mph1 helicases

et al. 2020

View full text Add to dashboard Cite

show abstract

“…In some circumstances, an alternative pathway resulting from the nuclease-dependent early cleavage of the D-loop can also generate crossovers [14][15][16][17]. A number of excellent reviews thoroughly covering all the mechanistic details of HR pathways are available [18][19][20][21][22][23]. Controlled disengagement of the joint molecule (JM) intermediates generated by HR must occur prior to chromosome segregation to guarantee the equal distribution of intact genomic information during cell division.…”

Section: Introductionmentioning

confidence: 99%

Resolvases, Dissolvases, and Helicases in Homologous Recombination: Clearing the Road for Chromosome Segregation

San-Segundo

Clemente‐Blanco

2020

Genes

View full text Add to dashboard Cite

The execution of recombinational pathways during the repair of certain DNA lesions or in the meiotic program is associated to the formation of joint molecules that physically hold chromosomes together. These structures must be disengaged prior to the onset of chromosome segregation. Failure in the resolution of these linkages can lead to chromosome breakage and nondisjunction events that can alter the normal distribution of the genomic material to the progeny. To avoid this situation, cells have developed an arsenal of molecular complexes involving helicases, resolvases, and dissolvases that recognize and eliminate chromosome links. The correct orchestration of these enzymes promotes the timely removal of chromosomal connections ensuring the efficient segregation of the genome during cell division. In this review, we focus on the role of different DNA processing enzymes that collaborate in removing the linkages generated during the activation of the homologous recombination machinery as a consequence of the appearance of DNA breaks during the mitotic and meiotic programs. We will also discuss about the temporal regulation of these factors along the cell cycle, the consequences of their loss of function, and their specific role in the removal of chromosomal links to ensure the accurate segregation of the genomic material during cell division.

show abstract

“…During repair, components of the DSBR complex scan for regions homologous to the damaged locus and fix the breaks via the formation of heteroduplexes and other unstable structures (18). The resolution of these temporary configurations can be neutral (non-crossover NAHR), or can lead to dramatic chromosomal rearrangements in the case of crossover between the recombined loci (19,20). NAHR with crossover can therefore disrupt the genetic information causing aberrant phenotypes; repeat elements have often been found at the breakpoints of NAHR events associated with cancer and genomic disorders caused by erroneous meiotic pairing (21)(22)(23).…”

Section: Introductionmentioning

confidence: 99%

Recombination of repeat elements generates somatic complexity in human genomes

Pascarella

Hashimoto

Busch

et al. 2020

Preprint

View full text Add to dashboard Cite

AbstractMillions of Alu and LINE-1 copies in our genomes contribute to evolution and genetic disorders via non-allelic homologous recombination (NAHR), but the somatic extent of these rearrangements has not been systematically investigated. Here we combined high-throughput capture and sequencing of repeat elements with a new bioinformatic pipeline to show that somatic NAHR of Alu and LINE-1 elements is common in human genomes. We describe tissue-specific hallmarks of NAHR, and show that retroelements acting as recombination hotspots are enriched in cancer genes and structural variants. Analysis of recombination in human induced pluripotent stem cells and differentiated neurons revealed a neuron-specific recombination signature suggesting that the emergence of cell type-specific recombination profiles accompanies cell-fate determination. Finally, we found that somatic NAHR profiles are altered in Parkinson’s and Alzheimer’s disease, indicating a link between retroelements recombination and genomic instability in neurodegeneration. This work shows that somatic recombination of repeat elements contributes massively to genomic diversity, and that extensive recombinogenic activity of retroelements may act as a grey eminence in the transition from health to disease.

show abstract

Moving forward one step back at a time: reversibility during homologous recombination

Cited by 42 publications

References 69 publications

Rad9/53BP1 promotes DNA repair via crossover recombination by limiting the Sgs1 and Mph1 helicases

Rad9/53BP1 promotes DNA repair via crossover recombination by limiting the Sgs1 and Mph1 helicases

Resolvases, Dissolvases, and Helicases in Homologous Recombination: Clearing the Road for Chromosome Segregation

Recombination of repeat elements generates somatic complexity in human genomes

Contact Info

Product

Resources

About