Carolyn Turcotte

All Publications

• Chromosome-specific differences in the recombination landscape of spontaneous meiotic nondisjunction GENETICS Turcotte, C. A., Sekelsky, J. 2026

  Abstract

  Failures in chromosome segregation during meiosis result in aneuploid gametes and are the leading cause of miscarriage. The position and number of crossovers, genetic exchanges between homologous chromosomes, are essential to their accurate disjunction in meiosis. Previous research analyzing nondisjunction of acro- and telocentric chromosomes in human and Drosophila has identified altered positioning and number of crossovers that differs between meiosis I and meiosis II nondisjunction. Limited data from positioning in chromosomes that segregated normally in metacentric trisomies has suggested discrepancies between the behavior of these chromosomes and the acro/telocentrics in nondisjunction, which warrants further investigation. Here, we employ whole-genome sequencing to study spontaneous meiotic nondisjunctionof the metacentric chromosome 2 in Drosophila melanogaster. Several patterns of recombination may differentially impact telo- versusmetacentric chromosomes: lack of a crossover, distal crossovers, and proximal crossovers. We find that unlike meiotic nondisjunction of the Drosophila X chromosome, nondisjunction of chromosome 2 is not associated with dramatic changes in crossover landscape, but is associated with reduced recombination. Differences in the proportions of NDJ events with altered recombination patterns between chromosomes X and 2 suggest that abnormal crossover positions disparately affect chromosomes with different shapes. Taken together, these findings highlight that the underlying triggers of meiotic nondisjunction are chromosome-specific.

  View details for DOI 10.1093/genetics/iyag076

  View details for Web of Science ID 001737047200001

  View details for PubMedID 41875372

• Meiotic Crossover Patterning FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY Pazhayam, N. M., Turcotte, C. A., Sekelsky, J. 2021; 9: 681123

  Abstract

  Proper number and placement of meiotic crossovers is vital to chromosome segregation, with failures in normal crossover distribution often resulting in aneuploidy and infertility. Meiotic crossovers are formed via homologous repair of programmed double-strand breaks (DSBs). Although DSBs occur throughout the genome, crossover placement is intricately patterned, as observed first in early genetic studies by Muller and Sturtevant. Three types of patterning events have been identified. Interference, first described by Sturtevant in 1915, is a phenomenon in which crossovers on the same chromosome do not occur near one another. Assurance, initially identified by Owen in 1949, describes the phenomenon in which a minimum of one crossover is formed per chromosome pair. Suppression, first observed by Beadle in 1932, dictates that crossovers do not occur in regions surrounding the centromere and telomeres. The mechanisms behind crossover patterning remain largely unknown, and key players appear to act at all scales, from the DNA level to inter-chromosome interactions. There is also considerable overlap between the known players that drive each patterning phenomenon. In this review we discuss the history of studies of crossover patterning, developments in methods used in the field, and our current understanding of the interplay between patterning phenomena.

  View details for DOI 10.3389/fcell.2021.681123

  View details for Web of Science ID 000683432700001

  View details for PubMedID 34368131

  View details for PubMedCentralID PMC8344875

• A pathway for error-free non-homologous end joining of resected meiotic double-strand breaks NUCLEIC ACIDS RESEARCH Hatkevich, T., Miller, D. E., Turcotte, C. A., Miller, M. C., Sekelsky, J. 2021; 49 (2): 879-890

  Abstract

  Programmed DNA double-strand breaks (DSBs) made during meiosis are repaired by recombination with the homologous chromosome to generate, at selected sites, reciprocal crossovers that are critical for the proper separation of homologs in the first meiotic division. Backup repair processes can compensate when the normal meiotic recombination processes are non-functional. We describe a novel backup repair mechanism that occurs when the homologous chromosome is not available in Drosophila melanogaster meiosis. In the presence of a previously described mutation (Mcm5A7) that disrupts chromosome pairing, DSB repair is initiated by homologous recombination but is completed by non-homologous end joining (NHEJ). Remarkably, this process yields precise repair products. Our results provide support for a recombination intermediate recently proposed in mouse meiosis, in which an oligonucleotide bound to the Spo11 protein that catalyzes DSB formation remains bound after resection. We propose that this oligonucleotide functions as a primer for fill-in synthesis to allow scarless repair by NHEJ. We argue that this is a conserved repair mechanism that is likely to be invoked to overcome occasional challenges in normal meiosis.

  View details for DOI 10.1093/nar/gkaa1205

  View details for Web of Science ID 000626723800026

  View details for PubMedID 33406239

  View details for PubMedCentralID PMC7826270

• Maintenance of Genome Integrity by Mi2 Homologs CHD-3 and LET-418 in <i>Caenorhabditis elegans</i> GENETICS Turcotte, C. A., Sloat, S. A., Rigothi, J. A., Rosenkranse, E., Northrup, A. L., Andrews, N. P., Checchi, P. M. 2018; 208 (3): 991-1007

  Abstract

  Meiotic recombination depends upon the tightly coordinated regulation of chromosome dynamics and is essential for the production of haploid gametes. Central to this process is the formation and repair of meiotic double-stranded breaks (DSBs), which must take place within the constraints of a specialized chromatin architecture. Here, we demonstrate a role for the nucleosome remodeling and deacetylase (NuRD) complex in orchestrating meiotic chromosome dynamics in Caenorhabditis elegans Our data reveal that the conserved Mi2 homologs Chromodomain helicase DNA-binding protein (CHD-3) and its paralog LET-418 facilitate meiotic progression by ensuring faithful repair of DSBs through homologous recombination. We discovered that loss of either CHD-3 or LET-418 results in elevated p53-dependent germ line apoptosis, which relies on the activation of the conserved checkpoint kinase CHK-1 Consistent with these findings, chd-3 and let-418 mutants produce a reduced number of offspring, indicating a role for Mi2 in forming viable gametes. When Mi2 function is compromised, persisting recombination intermediates are detected in late pachytene nuclei, indicating a failure in the timely repair of DSBs. Intriguingly, our data indicate that in Mi2 mutant germ lines, a subset of DSBs are repaired by nonhomologous end joining, which manifests as chromosomal fusions. We find that meiotic defects are exacerbated in Mi2 mutants lacking CKU-80, as evidenced by increased recombination intermediates, corpses, and defects in chromosomal integrity. Taken together, our findings support a model wherein the C. elegans Mi2 complex maintains genomic integrity through reinforcement of a chromatin landscape suitable for homology-driven repair mechanisms.

  View details for DOI 10.1534/genetics.118.300686

  View details for Web of Science ID 000426219600010

  View details for PubMedID 29339410

  View details for PubMedCentralID PMC5844346

• CRISPR Technology Reveals RAD(51)-ical Mechanisms of Repair in Roundworms: An Educational Primer for Use with "Promotion of Homologous Recombination by SWS-1 in Complex with RAD-51 Paralogs in <i>Caenorhabditis elegans</i>" GENETICS Turcotte, C. A., Andrews, N. P., Sloat, S. A., Checchi, P. M. 2016; 204 (3): 883-891

  Abstract

  The mechanisms cells use to maintain genetic fidelity via DNA repair and the accuracy of these processes have garnered interest from scientists engaged in basic research to clinicians seeking improved treatment for cancer patients. Despite the continued advances, many details of DNA repair are still incompletely understood. In addition, the inherent complexity of DNA repair processes, even at the most fundamental level, makes it a challenging topic. This primer is meant to assist both educators and students in using a recent paper, "Promotion of homologous recombination by SWS-1 in complex with RAD-51 paralogs in Caenorhabditis elegans," to understand mechanisms of DNA repair. The goals of this primer are to highlight and clarify several key techniques utilized, with special emphasis on the clustered, regularly interspaced, short palindromic repeats technique and the ways in which it has revolutionized genetics research, as well as to provide questions for deeper in-class discussion.

  View details for DOI 10.1534/genetics.116.195479

  View details for Web of Science ID 000388502900007

  View details for PubMedID 28114101

  View details for PubMedCentralID PMC5105866