PDBsum entry: 2htf

Transferase

PDB id: 2htf

Contents

Protein chain

105 a.a. *

* Residue conservation analysis

PDB id:

2htf

Name:

Transferase

Title:

The solution structure of the brct domain from human polymerase reveals homology with the tdt brct domain

Structure:

DNA polymerase mu. Chain: a. Fragment: brct domain. Synonym: pol mu. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: polm. Expressed in: escherichia coli. Expression_system_taxid: 562

NMR struc:

11 models

Authors:

E.F.Derose,M.W.Clarkson,S.A.Gilmore,D.A.Ramsden,G.A.Mueller, R.E.London,A.L.Lee

Key ref:

E.F.DeRose et al. (2007). Solution structure of polymerase mu's BRCT Domain reveals an element essential for its role in nonhomologous end joining. Biochemistry, 46, 12100-12110. PubMed id: 17915942 DOI: 10.1021/bi7007728

Date:

25-Jul-06 Release date: 27-Feb-07

Protein chain

Q9NP87  (DPOLM_HUMAN) -  DNA-directed DNA/RNA polymerase mu

Seq: 494 a.a.

Struc: 105 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.2.7.7.7 - DNA-directed Dna polymerase.
• Reaction: Deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 Gene Ontology (GO) functional annotation 

• Cellular component: intracellular (1 term)
• Biochemical function: DNA nucleotidylexotransferase activity (1 term)

reference

DOI no: 10.1021/bi7007728

Biochemistry 46:12100-12110 (2007)

PubMed id: 17915942

Solution structure of polymerase mu's BRCT Domain reveals an element essential for its role in nonhomologous end joining.

E.F.DeRose, M.W.Clarkson, S.A.Gilmore, C.J.Galban, A.Tripathy, J.M.Havener, G.A.Mueller, D.A.Ramsden, R.E.London, A.L.Lee.

ABSTRACT

The solution structure and dynamics of the BRCT domain from human DNA polymerase mu, implicated in repair of chromosome breaks by nonhomologous end joining (NHEJ), has been determined using NMR methods. BRCT domains are typically involved in protein-protein interactions between factors required for the cellular response to DNA damage. The pol mu BRCT domain is atypical in that, unlike other reported BRCT structures, the pol mu BRCT is neither part of a tandem grouping, nor does it appear to form stable homodimers. Although the sequence of the pol mu BRCT domain has some unique characteristics, particularly the presence of >10% proline residues, it forms the characteristic alphabetaalpha sandwich, in which three alpha helices are arrayed around a central four-stranded beta-sheet. The structure of helix alpha1 is characterized by two solvent-exposed hydrophobic residues, F46 and L50, suggesting that this element may play a role in mediating interactions of pol mu with other proteins. Consistent with this argument, mutation of these residues, as well as the proximal, conserved residue R43, specifically blocked the ability of pol mu to efficiently work together with NHEJ factors Ku and XRCC4-ligase IV to join noncomplementary ends together in vitro. The structural, dynamic, and biochemical evidence reported here identifies a functional surface in the pol mu BRCT domain critical for promoting assembly and activity of the NHEJ machinery. Further, the similarity between the interaction regions of the BRCT domains of pol mu and TdT support the conclusion that they participate in NHEJ as alternate polymerases.