Combined genetic and biochemical approaches to uncover and characterize redundant factors involved in late stages of recombinational repair. (360G-Wellcome-090944_Z_09_Z)

£1,427,423

Homologous Recombination (HR) provides an error free DNA repair pathway to deal with DNA double strand breaks (DSBs). Such breaks arise from genotoxic agents, but also happen during normal DNA replication. We know very little about late steps of HR, where redundant mechanisms seem to be able to resolve Holliday Junction (HJ) intermediates. It is only very recently that canonical HJ resolvases have been indentified in animals. One of those enzymes is GEN1 which was purified from human cell ext racts. However, its in vivo function remained unclear. Having followed a forward genetic approach, we found that the C. elegans homolog is required for DSB repair and unexpectedly also has a role in DNA damage checkpoint signalling. We propose a series of genetic screens to find further genes that act in the gen-1 DNA damage checkpoint and DSB repair pathways. Furthermore, we aim to undertake synthetic lethal screens to find genes that act in parallel to gen-1 to mediate the processing of late r ecombination intermediates. Finally, we hope to better understand how GEN-1 works by employing purification procedures from worms and from chicken DT40 cells. This cell-line will also be used to generalize genetic interactions and phenotypes we find in worms.

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Grant Details

Amount Awarded 1427423
Applicant Surname Gartner
Approval Committee Basic Science Interview Committee
Award Date 2010-03-22T00:00:00+00:00
Financial Year 2009/10
Grant Programme: Title Senior Research Fellowship Basic
Internal ID 090944/Z/09/Z
Lead Applicant Prof Anton Gartner
Partnership Value 1427423
Planned Dates: End Date 2015-07-31T00:00:00+00:00
Planned Dates: Start Date 2010-08-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region Scotland
Sponsor(s) Prof Angus Lamond