Loss of Drosophila Mei-41/ATR Alters Meiotic Crossover Patterning

Abstract

Meiotic crossovers must be properly patterned to ensure accurate disjunction of homologous chromosomes during meiosis I. Disruption of the spatial distribution of crossovers can lead to nondisjunction, aneuploidy, gamete dysfunction, miscarriage, or birth defects. One of the earliest identified genes involved in proper crossover patterning is , which encodes the ortholog of the checkpoint kinase ATR. Analysis of hypomorphic mutants suggested the existence of crossover patterning defects, but it was not possible to assess this in null mutants because of maternal-effect embryonic lethality. To overcome this lethality, we constructed null mutants in which we expressed wild-type Mei-41 in the germline after completion of meiotic recombination, allowing progeny to survive. We find that crossovers are decreased to about one-third of wild-type levels, but the reduction is not uniform, being less severe in the proximal regions of chromosome L than in medial or distalL or on the chromosome. None of the crossovers formed in the absence of Mei-41 require Mei-9, the presumptive meiotic resolvase, suggesting that Mei-41 functions everywhere, despite the differential effects on crossover frequency. Interference appears to be significantly reduced or absent in mutants, but the reduction in crossover density in centromere-proximal regions is largely intact. We propose that crossover patterning is achieved in a stepwise manner, with the crossover suppression related to proximity to the centromere occurring prior to and independently of crossover designation and enforcement of interference. In this model, Mei-41 has an essential function in meiotic recombination after the centromere effect is established but before crossover designation and interference occur.

The tumor suppressor BRCA1-BARD1 complex localizes to the synaptonemal complex and regulates recombination under meiotic dysfunction in Caenorhabditis elegans

“…See S1 Table for data used for calculations. Statistical analyses of interference using χ 2 on 2-by-2 contingency tables of observed and expected DCOs [ 119 ], indicated that interference in the CR interval fell short of statistical significance between zim-1 and brc-1(tm1145); zim-1 , p = 0.064.…”

“…Statistical analyses were performed using the two-tailed Fisher's Exact test, 95% C.I., as in [ 117 , 118 ]. For statistical analyses of interference we conducted χ 2 tests on 2-by-2 contingency tables of observed and expected DCOs [ 119 ].…”

Meiosis Progression and Recombination in Holocentric Plants: What Is Known?

“…If we look at other well-studied model eukaryotes, the centromere effect appears to be highly conserved and also very efficient in avoiding COs in pericentromeric regions. In Drosophila melanogaster the DSB landscape appears to be flat along the chromosome arm, but downstream recombination is then affected by the centromere effect that eliminates pericentromeric recombination intermediates and models the recombination pattern (Hatkevich et al, 2017;Brady et al, 2018). In maize the centromeric effect seems to work with a different mechanism but with the same result.…”

Separable roles of the DNA damage response kinase Mec1(ATR) and its activator Rad24(RAD17) within the regulation of meiotic recombination

“…ATR deletion in male mice causes fragmentation of the chromosome axis, and ATR is required for synapsis and loading of recombinases RAD51 and DMC1 at DSB sites [21,22]. In Drosophila , loss of Mei-41, the fly ATR orthologue, not only abrogates checkpoint signalling [23], but also alters the frequency and spatial distribution of COs [24]. In Arabidopsis thaliana , although atr mutants are fully fertile [25], ATR promotes meiotic recombination by regulating the deposition of DMC1 at DSBs [26].…”