TY - JOUR
T1 - Kinetochores, cohesin, and DNA breaks
T2 - Controlling meiotic recombination within pericentromeres
AU - Kuhl, Lisa Marie
AU - Vader, Gerben
PY - 2019/3
Y1 - 2019/3
N2 - In meiosis, DNA break formation and repair are essential for the formation of crossovers between homologous chromosomes. Without crossover formation, faithful meiotic chromosome segregation and sexual reproduction cannot occur. Crossover formation is initiated by the programmed, meiosis-specific introduction of numerous DNA double-strand breaks, after which specific repair pathways promote recombination between homologous chromosomes. Despite its crucial nature, meiotic recombination is fraud with danger: When positioned or repaired inappropriately, DNA breaks can have catastrophic consequences on genome stability of the resulting gametes. As such, DNA break formation and repair needs to be carefully controlled. Within centromeres and surrounding regions (i.e., pericentromeres), meiotic crossover recombination is repressed in organisms ranging from yeast to humans, and a failure to do so is implicated in chromosome missegregation and developmental aneuploidy. (Peri)centromere sequence identity and organization diverge considerably across eukaryotes, yet suppression of meiotic DNA break formation and repair appear universal. Here, we discuss emerging work that has used budding and fission yeast systems to study the mechanisms underlying pericentromeric suppression of DNA break formation and repair. We particularly highlight a role for the kinetochore, a universally conserved, centromere-associated structure essential for chromosome segregation, in suppressing (peri)centromeric DNA break formation and repair. We discuss the current understanding of kinetochore-associated and chromosomal factors involved in this regulation and suggest future avenues of research.
AB - In meiosis, DNA break formation and repair are essential for the formation of crossovers between homologous chromosomes. Without crossover formation, faithful meiotic chromosome segregation and sexual reproduction cannot occur. Crossover formation is initiated by the programmed, meiosis-specific introduction of numerous DNA double-strand breaks, after which specific repair pathways promote recombination between homologous chromosomes. Despite its crucial nature, meiotic recombination is fraud with danger: When positioned or repaired inappropriately, DNA breaks can have catastrophic consequences on genome stability of the resulting gametes. As such, DNA break formation and repair needs to be carefully controlled. Within centromeres and surrounding regions (i.e., pericentromeres), meiotic crossover recombination is repressed in organisms ranging from yeast to humans, and a failure to do so is implicated in chromosome missegregation and developmental aneuploidy. (Peri)centromere sequence identity and organization diverge considerably across eukaryotes, yet suppression of meiotic DNA break formation and repair appear universal. Here, we discuss emerging work that has used budding and fission yeast systems to study the mechanisms underlying pericentromeric suppression of DNA break formation and repair. We particularly highlight a role for the kinetochore, a universally conserved, centromere-associated structure essential for chromosome segregation, in suppressing (peri)centromeric DNA break formation and repair. We discuss the current understanding of kinetochore-associated and chromosomal factors involved in this regulation and suggest future avenues of research.
KW - (peri)centromeres
KW - cohesin
KW - DNA breaks
KW - kinetochore
KW - meiotic recombination
KW - Saccharomyces
KW - Schizosaccharomyces
UR - http://www.scopus.com/inward/record.url?scp=85061199662&partnerID=8YFLogxK
U2 - 10.1002/yea.3366
DO - 10.1002/yea.3366
M3 - Article
C2 - 30625250
AN - SCOPUS:85061199662
VL - 36
SP - 121
EP - 127
JO - Yeast
JF - Yeast
SN - 0749-503X
IS - 3
ER -