期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 115, 期 40, 页码 E9333-E9342出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1801920115
关键词
meiosis; crossover interference; DNA break interference; DSB hotspot clustering; S. pombe
资金
- NIH [R01 GM031693, R01 GM032194, R35 GM118120, P30 CA015704]
- NATIONAL CANCER INSTITUTE [P30CA015704] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM031693, R35GM118120, R01GM032194] Funding Source: NIH RePORTER
Viable gamete formation requires segregation of homologous chromosomes connected, in most species, by cross-overs. DNA double-strand break (DSB) formation and the resulting cross-overs are regulated at multiple levels to prevent overabundance along chromosomes. Meiotic cells coordinate these events between distant sites, but the physical basis of long-distance chromosomal communication has been unknown. We show that DSB hotspots up to -200 kb (similar to 35 cM) apart form clusters via hotspot-binding proteins Rec25 and Rec27 in fission yeast. Clustering coincides with hotspot competition and interference over similar distances. Without Tell (an ATM tumor-suppressor homolog), DSB and crossover interference become negative, reflecting coordinated action along a chromosome. These results indicate that DSB hotspots within a limited chromosomal region and bound by their protein determinants form a clustered structure that, via Tell, allows only one DSB per region. Such a roulette process within clusters explains the observed pattern of crossover interference in fission yeast. Key structural and regulatory components of clusters are phylogenetically conserved, suggesting conservation of this vital regulation. Based on these observations, we propose a model and discuss variations in which clustering and competition between DSB sites leads to DSB interference and in turn produces crossover interference.
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