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the structure, which are near the hinges or domain boundaries and which should affect the<br />

motional characteristics.<br />

DNA polymerase β<br />

HAG hinges: 88-89,263-264<br />

The base excision repair pathway responds to oxidative or alkylation damage to DNA,<br />

removing on the order of 10,000 lesions per cell per day and is one of several DNA repair<br />

processes necessary for the survival of eukaryotic cells. This process begins with<br />

recognition of the damaged site by a specific glycosylase, which then removes the<br />

offending base. An apurimic/apyrimidimic exonuclease removes the backbone sugar-<br />

phosphate backbone. DNA polymerase β (pol β) then fills in the resulting gap and DNA<br />

ligase completes the repair by healing the nicked backbone.<br />

Structurally, Pol β resembles a hand, with so-named fingers, palm, and thumb<br />

subdomains. Four metal ion binding sites exist. Two are in helix-hairpin-helix motifs<br />

away from the active site and associate directly with the DNA backbone, while the other<br />

two are involved in catalysis. It has a hinge between the catalytic (palm) domain<br />

(residues 149-262) and the C-terminal (thumb) domain (residues 263-338), both of which<br />

form part of a large active site cleft. The hinge region consists of a stretch of<br />

hydrophobic residues which appear to play a role in substrate recognition, since<br />

mutations of residue 260 result in an inaccurate polymerase.<br />

208

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