4LZG

Binary complex of human DNA Polymerase Mu with DNA

Summary for 4LZG

• Entry DOI: 10.2210/pdb4lzg/pdb
• Related: 2IHM 4LZD 4M04 4M0A
• Descriptor: DNA-directed DNA/RNA polymerase mu, template strand, upstream primer strand, ... (8 entities in total)
• Functional Keywords: polymerase, dna break repair, transferase-dna complex, transferase/dna
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus (By similarity): Q9NP87
• Total number of polymer chains: 4
• Total formula weight: 45386.87

Authors

Moon, A.F.,Pryor, J.M.,Ramsden, D.A.,Kunkel, T.A.,Bebenek, K.,Pedersen, L.C. (deposition date: 2013-07-31, release date: 2014-02-05, Last modification date: 2024-04-03)

Primary citation

Moon, A.F.,Pryor, J.M.,Ramsden, D.A.,Kunkel, T.A.,Bebenek, K.,Pedersen, L.C.
Sustained active site rigidity during synthesis by human DNA polymerase mu.
Nat.Struct.Mol.Biol., 21:253-260, 2014

PubMed Abstract: DNA polymerase μ (Pol μ) is the only template-dependent human DNA polymerase capable of repairing double-strand DNA breaks (DSBs) with unpaired 3' ends in nonhomologous end joining (NHEJ). To probe this function, we structurally characterized Pol μ's catalytic cycle for single-nucleotide incorporation. These structures indicate that, unlike other template-dependent DNA polymerases, Pol μ shows no large-scale conformational changes in protein subdomains, amino acid side chains or DNA upon dNTP binding or catalysis. Instead, the only major conformational change is seen earlier in the catalytic cycle, when the flexible loop 1 region repositions upon DNA binding. Pol μ variants with changes in loop 1 have altered catalytic properties and are partially defective in NHEJ. The results indicate that specific loop 1 residues contribute to Pol μ's unique ability to catalyze template-dependent NHEJ of DSBs with unpaired 3' ends.

PubMed: 24487959
DOI: 10.1038/nsmb.2766

Experimental method

X-RAY DIFFRACTION (1.599 Å)