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Sulfolobus SSB - linking DNA Repair and Transcription

Reference	BB/C000110/1
Principal Investigator / Supervisor	Prof. Malcolm White
Co-Investigators / Co-Supervisors
Institution	University of St Andrews
Department	Biology
Funding type	Research
Value (£)	422,446
Status	Completed
Type	Research Grant
Start date	01/08/2004
End date	30/11/2009
Duration	64 months

Abstract

Our laboratory is engaged in the study of DNA repair in the archaea. Little work has been done in this area, and many important questions remain unanswered. The archaea clearly have strong similarities to eukarya in their DNA repair pathways, as judged by bioinformatic analyses and biochemical and structural studies by ourselves and other laboratories. However, many key proteins, for example damage sensing proteins for mismatch repair and excision repair, are not evident in archaeal genomes. There are also some repair proteins unique to archaea. An example is the Holliday junction resolving enzyme Hjc, but there are doubtless many others to be discovered. Our preliminary evidence suggests that thermophilic archaea may express repair proteins constitutively, unlike both the bacteria and eukarya. There is also the possibility that studies of archaeal repair pathways may uncover as yet unidentified orthologues in eukarya, with important implications for human DNA repair. We request a continuation of BBSRC funding to study the single stranded DNA binding protein (SSB) from Sulfolobus solfataricus. SSB is the only recognisable damage recognition protein in Sulfolobus. We have made very good progress on the structure and function of this protein. Our first objective is to examine its role in DNA damage recognition and recruitment of repair proteins in more detail. We have recently uncovered an unexpected role for the SSB protein in the initiation of archaeal transcription. SSB interacts physically with RNA polymerase, and can support transcription in vitro in the absence of the TATA-binding protein TBP. SSB is also required for transcription in vitro from templates reconstituted as archaeal chromatin. Our second objective is to investigate and define this role of SSB in more detail, and to assess its relevance in vivo. DNA repair and transcription are intimately linked in bacteria and eukarya, but no one has looked for these links in archaea. Our third objective is to examine archaeal Transcription Coupled Repair (TCR). We will determine whether RNA polymerase stalls at a defined DNA lesion during transcription, and if so whether specific proteins are required to release the polymerase prior to repair (as is the case in bacteria), or whether excision repair can accommodate a stalled polymerase protein (as is the case in eukarya).

Summary

unavailable

Committee	Closed Committee - Biochemistry & Cell Biology (BCB)
Research Topics	Microbiology
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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