Wellcome Trust Clinical PhD Programme at the University of Dundee: 'Functional analysis of the SLX4 regulator of DNA repair nucleases.' (360G-Wellcome-093992_Z_10_Z)
SLX4 is a highly conserved scaffold protein that binds to, and is thought to regulate, three structure specific endonucleases (SSEs), XPF, MUS81 and SLX1, that play key roles in DNA repair. Depletion of SLX4 from human cells, or a biallelic mutation of SLX4 in cells from a Fanconi Anaemia patient, causes double strand break susceptibility and major DNA repair defects. This is thought to reflect a role for the SLX4 complex in processing branched DNA substrates that arise in DNA repair. SLX4 function is poorly understood at the molecular level. Human SLX4 has several modular domains including a BTB domain. BTB domains mediate protein oligomerization or alternatively binding to cullins. My first aim is to characterise the function of the SLX4 BTB domain. Also, SLX4 forms discrete constitutive subnuclear foci in cells in the absence of DNA damage, and these foci colocalise with XPF. In a Fanconi anaemia patient with low levels of SLX4 protein, XPF foci are absent. This indicates SLX4 localises XPF to nuclear foci in vivo. My second aim is to determine the nature and functional significance of SLX foci.
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Grant Details
Amount Awarded | 220113 |
Applicant Surname | Wilson |
Approval Committee | Neurosciences And Mental Health |
Award Date | 2010-08-31T00:00:00+00:00 |
Financial Year | 2009/10 |
Grant Programme: Title | PhD Training Fellowship for Clinicians |
Internal ID | 093992/Z/10/Z |
Lead Applicant | Dr Jamie Wilson |
Partnership Value | 220113 |
Planned Dates: End Date | 2013-09-05T00:00:00+00:00 |
Planned Dates: Start Date | 2010-09-06T00:00:00+00:00 |
Recipient Org: Country | United Kingdom |
Region | Scotland |
Sponsor(s) | Prof Doreen Cantrell |