Germline mutagenesis at recombination hotspots
Active Project Grant Awarded Last action
- Award ID
- R35GM157077
- Recipient
-
Regents Of The University Of Michigan UEI GNJ7BBP73WE9
- Awarding agency
-
National Institute of General Medical Sciences
National Institutes of Health, Department of Health and Human Services
- Obligated
- $1,103,435
Award facts
- Assistance listing
- 93.859 Biomedical Research and Research Training
- Completion date 35% complete
- Place of performance
- Ann Arbor, MI 48109, USA
Award details come from USAspending.gov.
Description
- Abstract
- Germline DE novo mutations impact human health and drive genome evolution. Among variants, little is known about DE novo structural variants (SVS) that are rare and difficult to identify, but can affect genome integrity more than point mutations due to their larger size (≥50 BP). Furthermore, how DE novo SVS originate in the germline is not fully understood. Meiosis is a potential source, because of the abundance of DNA double-strand breaks (dsbs) that are deliberately formed by the SPO11 protein to initiate meiotic recombination. While recombination ensures the reductional division of diploid cells and thus is essential for the formation of haploid gametes, dsbs are intrinsically mutagenic. My research program will address the mechanisms and factors that promote aberrant repair at meiotic dsbs, resulting in genome alterations. We recently discovered in mice that closely spaced dsbs (double cuts) can undergo end joining, leading to DE novo SVS, including deletions and tandem duplications. These events are rare in normal meiosis, but arise more frequently in the absence of the ATM kinase, which has a conserved role in regulating dsbs. Many genomic locations are at risk for end joining, as meiotic dsbs are formed at hotspots, many of which are separated by short genomic distances (
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $38,050 | |
| Amendment | $342,445 | |
| Amendment | $342,445 | |
| Original award | $380,495 |
Quick answers
Who received award R35GM157077?
R35GM157077 was awarded to Regents Of The University Of Michigan by National Institute of General Medical Sciences (National Institutes of Health) on February 1, 2025.
How much is award R35GM157077 worth?
$1,103,435 has been obligated on R35GM157077.
On GovTribe
See this award's full record
- Every transaction and subaward
- The recipient's other awards and teaming partners
- Similar grant awards
- Ask GovTribe AI about this award