4lzd

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Human DNA polymerase mu- Apoenzyme

Structural highlights

4lzd is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.849Å
Ligands:CL, EDO, IMD, NA
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

DPOLM_HUMAN Gap-filling polymerase involved in repair of DNA double-strand breaks by non-homologous end joining (NHEJ). Participates in immunoglobulin (Ig) light chain gene rearrangement in V(D)J recombination.[1] [2] [3] [4]

Publication Abstract from PubMed

DNA polymerase mu (Pol mu) 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 mu's catalytic cycle for single-nucleotide incorporation. These structures indicate that, unlike other template-dependent DNA polymerases, Pol mu 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 mu 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 mu's unique ability to catalyze template-dependent NHEJ of DSBs with unpaired 3' ends.

Sustained active site rigidity during synthesis by human DNA polymerase mu.,Moon AF, Pryor JM, Ramsden DA, Kunkel TA, Bebenek K, Pedersen LC Nat Struct Mol Biol. 2014 Mar;21(3):253-60. doi: 10.1038/nsmb.2766. Epub 2014 Feb, 2. PMID:24487959[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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Citations
13 reviews cite this structure
Non-homologous DNA end joining and alternative pathways to double-strand break repair.
Chang et al. (2017)
12 more
24 other articles
No citations found

See Also

References

  1. ↑ Nick McElhinny SA, Ramsden DA. Polymerase mu is a DNA-directed DNA/RNA polymerase. Mol Cell Biol. 2003 Apr;23(7):2309-15. PMID:12640116
  2. ↑ Ruiz JF, Juarez R, Garcia-Diaz M, Terrados G, Picher AJ, Gonzalez-Barrera S, Fernandez de Henestrosa AR, Blanco L. Lack of sugar discrimination by human Pol mu requires a single glycine residue. Nucleic Acids Res. 2003 Aug 1;31(15):4441-9. PMID:12888504
  3. ↑ Capp JP, Boudsocq F, Besnard AG, Lopez BS, Cazaux C, Hoffmann JS, Canitrot Y. Involvement of DNA polymerase mu in the repair of a specific subset of DNA double-strand breaks in mammalian cells. Nucleic Acids Res. 2007;35(11):3551-60. Epub 2007 May 5. PMID:17483519 doi:http://dx.doi.org/10.1093/nar/gkm243
  4. ↑ DeRose EF, Clarkson MW, Gilmore SA, Galban CJ, Tripathy A, Havener JM, Mueller GA, Ramsden DA, London RE, Lee AL. Solution structure of polymerase mu's BRCT Domain reveals an element essential for its role in nonhomologous end joining. Biochemistry. 2007 Oct 30;46(43):12100-10. Epub 2007 Oct 4. PMID:17915942 doi:10.1021/bi7007728
  5. ↑ Moon AF, Pryor JM, Ramsden DA, Kunkel TA, Bebenek K, Pedersen LC. Sustained active site rigidity during synthesis by human DNA polymerase mu. Nat Struct Mol Biol. 2014 Mar;21(3):253-60. doi: 10.1038/nsmb.2766. Epub 2014 Feb, 2. PMID:24487959 doi:http://dx.doi.org/10.1038/nsmb.2766

Contents


PDB ID 4lzd

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