Targeting of somatic hypermutation by the interplay of transcriptional kinetics and DNA repair fidelity
Public support
Provider
Czech Science Foundation
Programme
Standard projects
Call for proposals
SGA0202600001
Main participants
Ústav molekulární genetiky AV ČR, v. v. i.
Contest type
VS - Public tender
Contract ID
26-23400S
Alternative language
Project name in Czech
Targeting of somatic hypermutation by the interplay of transcriptional kinetics and DNA repair fidelity
Annotation in Czech
Somatic hypermutation (SHM) is a key process in diversification of antibodies. This process is initiated by cytosine deamination by the activation-induced cytidine deaminase (AID) and completed by error-prone processing of the resulting uracils. Although SHM aims primarily to Ig loci, frequent targeting of non-Ig loci has been reported, accentuating the role of SHM in lymphomagenesis. We developed a series of novel methods providing data on SHM susceptibility in the B cell genome and identifying a series of factors involved in SHM. Based on our preliminary results, we propose a model of SHM targeting that combines the roles of AID access to various genomic regions and site-specific variability of error-proneness of DNA repair. Our novel approach will decipher the transcriptional kinetic features involved in targeting of AID activity and identify factors responsible for specific distribution of cytidine deamination and high error rate of DNA repair in SHM-targeted regions. Our study will provide a novel insight into the mechanism of SHM targeting and its involvement in lymphomagenesis
Scientific branches
R&D category
ZV - Basic research
OECD FORD - main branch
30102 - Immunology
OECD FORD - secondary branch
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OECD FORD - another secondary branch
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CEP - equivalent branches <br>(according to the <a href="http://www.vyzkum.cz/storage/att/E6EF7938F0E854BAE520AC119FB22E8D/Prevodnik_oboru_Frascati.pdf">converter</a>)
EC - Immunology
Solution timeline
Realization period - beginning
Jan 1, 2026
Realization period - end
Dec 31, 2028
Project status
Z - Beginning multi-year project
Latest support payment
—
Data delivery to CEP
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data delivery code
CEP26-GA0-GA-R
Data delivery date
Apr 27, 2026
Finance
Total approved costs
8,968 thou. CZK
Public financial support
8,968 thou. CZK
Other public sources
0 thou. CZK
Non public and foreign sources
0 thou. CZK