Chromosome architecture and homologous recombination in meiosis

Ito, Masaru; Shinohara, Atsushi

doi:10.3389/fcell.2022.1097446

Cited by 22 publications

(17 citation statements)

References 177 publications

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“…STAG2 mutations are associated with DNA damage repair defects and aneuploidy in numerous cancer types 38,39,40 . Ubiquitination modulates cohesin function during meiosis and mitosis 41,42,43 , and further work is needed to elucidate the role of PRAME-mediated ubiquitination in tumorigenesis.…”

Section: Prame Misexpression Appears To Induce These Genomic Aberrati...mentioning

confidence: 99%

PRAME induces genomic instability in uveal melanoma

Harbour

Kurtenbach

Sánchez

et al. 2023

Preprint

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PRAME is a CUL2 ubiquitin ligase subunit that is normally expressed in the testis but becomes aberrantly overexpressed in many cancer types in association with aneuploidy and metastasis. Here, we show that PRAME is expressed predominantly in spermatogonia around the time of meiotic crossing-over in coordination with genes mediating DNA double strand break repair. Expression of PRAME in somatic cells upregulates pathways involved in meiosis, chromosome segregation and DNA repair, and it leads to increased DNA double strand breaks, telomere dysfunction and aneuploidy in neoplastic and non-neoplastic cells. This effect is mediated at least in part by ubiquitination of SMC1A and altered cohesin function. PRAME expression renders cells susceptible to inhibition of PARP1/2, suggesting increased dependence on alternative base excision repair pathways. These findings reveal a distinct oncogenic function of PRAME than can be targeted therapeutically in cancer.

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Section: Prame Misexpression Appears To Induce These Genomic Aberrati...mentioning

confidence: 99%

PRAME induces genomic instability in uveal melanoma

Harbour

Kurtenbach

Sánchez

et al. 2023

Preprint

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Section: Introductionmentioning

confidence: 99%

“…These morphology changes are mediated in large part by proteins of the meiotic chromosome axis, or axial element. Axis proteins bind replicated chromosomes to organize each chromosome into a linear array of chromatin loops and help activate, distribute, and resolve meiotic recombination events 3–5 . The axis comprises three main components: (1) cohesin complexes with one or more meiosis-specific subunits 6 ; (2) filamentous axis core proteins 7; and (3) meiotic HORMA domain (HORMAD) proteins 8,9 .…”

Section: Introductionmentioning

confidence: 99%

Chromatin binding by HORMAD proteins regulates meiotic recombination initiation

Milano

et al. 2023

Preprint

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The meiotic chromosome axis coordinates chromosome organization and interhomolog recombination in meiotic prophase and is essential for fertility. InS. cerevisiae, the HORMAD protein Hop1 mediates enrichment of axis proteins at nucleosome-rich genomic islands through a central chromatin-binding region (CBR). Here, we use cryoelectron microscopy to show that the Hop1 CBR directly recognizes bent nucleosomal DNA through a composite interface in its PHD and winged helix-turn-helix domains. Targeted disruption of the Hop1 CBR-nucleosome interface causes loss of axis proteins from nucleosome-rich islands, reduces meiotic DNA double-strand breaks (DSBs), and leads to defects in chromosome synapsis. Synthetic effects with the disassemblase Pch2 suggest that nucleosome binding delays a conformational switch in Hop1 from a DSB-promoting, Pch2-inaccessible state to a DSB-inactive, Pch2-accessible state to regulate the extent of meiotic DSB formation. Phylogenetic analyses of meiotic HORMADs reveal an ancient origin of this domain, suggesting that these mechanisms are broadly conserved.

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“…Homologous recombination, specifically crossing-over, is essential for chromosome segregation of homologous chromosomes during meiosis I. To ensure the crossover (CO) formation in meiosis, highly programmed regulation is implanted on the recombination pathway [37][38][39] . A meiosis-specific RAD51 cousin, DMC1, is critical for homology search in meiotic recombination in many species 40 .…”

Section: Introductionmentioning

confidence: 99%

FIGNL1 AAA+ ATPase remodels RAD51 and DMC1 filaments in pre-meiotic DNA replication and meiotic recombination

Ito

Furukohri

Matsuzaki

et al. 2023

Preprint

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The formation of RAD51/DMC1 filaments on single-stranded (ss)DNAs, which is essential for homology search and strand exchange in DNA double-strand break (DSB) repair and for the protection of stalled DNA replication forks, is tightly regulated in time and space. FIGNL1 AAA+++ ATPase plays positive and negative roles in the RAD51-mediated recombination in human cells. However, the role of FIGNL1 in gametogenesis remains unsolved. Here, we characterized a germ-line-specific conditional knockout (cKO) mouse of FIGNL1. The Fignl1 cKO male mice showed defective chromosome synapsis and impaired meiotic DSB repair with the accumulation of RAD51/DMC1 on chromosomes in mid-meiotic prophase I, supporting a role of FIGNL1 in a post-assembly stage of RAD51/DMC1 filaments. Fignl1 cKO spermatocytes accumulate RAD51 and DMC1 ensembles on chromosomes not only in early meiotic prophase I but also in meiotic S-phase. These RAD51/DMC1 assemblies are independent of meiotic DSB formation. Finally, we showed that purified FIGNL1 dismantles RAD51 filament on double-stranded (ds)DNA as well as ssDNA. These results suggest a critical role of FIGNL1 to limit the uncontrolled assembly of RAD51 and DMC1 on native dsDNAs during the meiotic S-phase and meiotic prophase I.

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Chromosome architecture and homologous recombination in meiosis

Cited by 22 publications

References 177 publications

PRAME induces genomic instability in uveal melanoma

PRAME induces genomic instability in uveal melanoma

Chromatin binding by HORMAD proteins regulates meiotic recombination initiation

FIGNL1 AAA+ ATPase remodels RAD51 and DMC1 filaments in pre-meiotic DNA replication and meiotic recombination

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