3SI8: Human Dna Polymerase Eta - Dna Ternary Complex With The 5't Of A Cpd In The Active Site (Tt2)

Citation:
Abstract
The variant form of the human syndrome xeroderma pigmentosum (XPV) is caused by a deficiency in DNA polymerase eta (Poleta), a DNA polymerase that enables replication through ultraviolet-induced pyrimidine dimers. Here we report high-resolution crystal structures of human Poleta at four consecutive steps during DNA synthesis through cis-syn cyclobutane thymine dimers. Poleta acts like a 'molecular splint' to stabilize damaged DNA in a normal B-form conformation. An enlarged active site accommodates the thymine dimer with excellent stereochemistry for two-metal ion catalysis. Two residues conserved among Poleta orthologues form specific hydrogen bonds with the lesion and the incoming nucleotide to assist translesion synthesis. On the basis of the structures, eight Poleta missense mutations causing XPV can be rationalized as undermining the molecular splint or perturbing the active-site alignment. The structures also provide an insight into the role of Poleta in replicating through D loop and DNA fragile sites.
PDB ID: 3SI8Download
MMDB ID: 92387
PDB Deposition Date: 2011/6/17
Updated in MMDB: 2011/08
Experimental Method:
x-ray diffraction
Resolution: 2.15  Å
Source Organism:
synthetic construct
Similar Structures:
Biological Unit for 3SI8: trimeric; determined by author and by software (PISA)
Molecular Components in 3SI8
Label Count Molecule
Protein (1 molecule)
1
DNA Polymerase ETA(Gene symbol: POLH)
Molecule annotation
Nucleotides(2 molecules)
1
DNA (5'-d(*tp*a*ap*cp*(ttd)p*ap*tp*gp*ap*cp*gp*c)-3')
Molecule annotation
1
DNA (5'-d(*tp*gp*cp*gp*tp*cp*ap*tp*a)-3')
Molecule annotation
Chemicals (20 molecules)
1
1
2
8
3
1
4
2
5
5
6
2
7
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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