Transport and signalling of cell adhesion molecules and their role in motor neuron survival. (360G-Wellcome-080510_Z_06_B)

£5,565

We previously demonstrated that histone H2A is phosphorylated at Ser129 in response to DNA damage by the Mec1p and Tel1p kinases in yeast. Others demonstrated that the analogous residue in mammalian chromatin (Ser139 on histone H2AX) is also phosphorylated in response to DNA damage, and H2AX is a tumour suppressor gene in mice, demonstrating that this is a central event in eukaryotic DNA damage responses. Yet, it is still not entirely clear how this phosphorylation event functions to facilitate survival after DNA damage occurs. We therefore propose to further investigate the function of H2A phosphorylation using three approaches. First, we will systematically characterize the phosphorylation event by analyzing the timing, kinetics, and genetic dependence of phosphorylation in different cell cycle phases, growth phases and ploidy backgrounds. Second, we will examine the fate of phosphorylated H2A. Third, we plan to investigate the effect of phoshpoinositol signalling on H2A phosphorylation and DNA damage responses. Finally, we will integrate these studies with ongoing research in the lab in which we have identified proteins that bind specifically to phosphorylated H2A. Together, these studies will advance our understanding of this highly conserved event in particular and of DNA damage responses in general.

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Grant Details

Amount Awarded 5565
Applicant Surname Wade
Approval Committee Neurosciences And Mental Health
Award Date 2010-07-13T00:00:00+00:00
Financial Year 2009/10
Grant Programme: Title PhD Studentship (Basic)
Internal ID 080510/Z/06/B
Lead Applicant Ms Anna Wade
Partnership Value 5565
Planned Dates: End Date 2010-12-31T00:00:00+00:00
Planned Dates: Start Date 2010-10-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region Greater London
Sponsor(s) Prof David Attwell