Chromosome organization in development and adulthood
Active Project Grant Awarded Last action
- Award ID
- R16GM153517
- Recipient
-
Sonoma State University UEI GZ6NCMJFL6R4
- Awarding agency
-
National Institute of General Medical Sciences
National Institutes of Health, Department of Health and Human Services
- Obligated
- $443,700
Award facts
- Assistance listing
- 93.859 Biomedical Research and Research Training
- Completion date 60% complete
- Place of performance
- Rohnert Park, CA 94928, USA
Award details come from USAspending.gov.
Description
- Abstract
- The long-term goal of the study is to uncover how human somatic cells regulate proper chromosome organization during development. While pairing of homologous chromosomes can drive meiotic recombination, mitotic pairing can lead to detrimental consequences such as allelic MIS-regulation and genome instability in humans. However, IT remains largely unknown how mitotic pairing and recombination, is prevented in somatic cells to avoid genomic instability during continuous cellular division in development. We have recently revealed that: (a) dividing human primary cells keep two haploid chromosome sets apart to either side of the centrosome, or nuclear division axis; (b) a diminished zone, devoid of interchromosomal linkage components, is present along the centrosome axis, forming the boundary between the two haploid sets; (c) simultaneous tracking of individual chromosome oscillation and the spindle axis, demonstrates ipsilateral restriction of chromosome movement of two chromosome sets from mitosis onset to G1 interphase; (d) high resolution imaging of a translocation mouse with a supernumerary chromosome reveals that a maternally derived chromosome is positioned to a haploid set based on parental origin; and (e) this haploid set-based anti-pairing motif is lost in renal carcinoma cells. These findings reveal a new model wherein somatic cells impede homologous chromosome pairing by keeping two haploid chromosome sets apart along a diminished zone of interchromosomal linkage components, coincident with the centrosome axis. The model predicts that compartmentalization of the individual haploid sets from each other require biophysical inter-chromosomal linkage properties within a haploid set, along with an association between the two haploid sets. Anti-pairing of homologous chromosomes is essential for genetic stability and function in human cells, thus, we predict that the spatial segregation of haploid sets is conserved among all cell types. Our proposal aims to experimentally test these hypotheses. Successful outcomes of this comprehensive study will generate new mechanistic information for how anti-pairing of homologs is achieved, maintained, and regulated throughout the cell cycle. These results would allow US investigate the significance of higher-order chromosome organization in cellular development that will be critically important for elucidating new mechanisms of human disease.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $147,900 | |
| Amendment | $147,900 | |
| Original award | $147,900 |
Quick answers
Who received award R16GM153517?
R16GM153517 was awarded to Sonoma State University by National Institute of General Medical Sciences (National Institutes of Health) on June 15, 2024.
How much is award R16GM153517 worth?
$443,700 has been obligated on R16GM153517.
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