| Structural highlights
5tyy is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , , , , |
| Related: | 5txx, 5txz, 5tyb, 5tyc, 5tyd, 5tye, 5tyf, 5tyg, 5tyu, 5tyv, 5tyw, 5tyx, 5tyz |
| Gene: | POLM, polmu (HUMAN) |
| Activity: | DNA-directed DNA polymerase, with EC number 2.7.7.7 |
| 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 (pol) mu is a DNA-dependent polymerase that incorporates nucleotides during gap-filling synthesis in the non-homologous end-joining pathway of double-strand break repair. Here we report time-lapse X-ray crystallography snapshots of catalytic events during gap-filling DNA synthesis by pol mu. Unique catalytic intermediates and active site conformational changes that underlie catalysis are uncovered, and a transient third (product) metal ion is observed in the product state. The product manganese coordinates phosphate oxygens of the inserted nucleotide and PPi. The product metal is not observed during DNA synthesis in the presence of magnesium. Kinetic analyses indicate that manganese increases the rate constant for deoxynucleoside 5'-triphosphate insertion compared to magnesium. The likely product stabilization role of the manganese product metal in pol mu is discussed. These observations provide insight on structural attributes of this X-family double-strand break repair polymerase that impact its biological function in genome maintenance.DNA polymerase (pol) mu functions in DNA double-strand break repair. Here the authors use time-lapse X-ray crystallography to capture the states of pol micro during the conversion from pre-catalytic to product complex and observe a third transiently bound metal ion in the product state.
Time-lapse crystallography snapshots of a double-strand break repair polymerase in action.,Jamsen JA, Beard WA, Pedersen LC, Shock DD, Moon AF, Krahn JM, Bebenek K, Kunkel TA, Wilson SH Nat Commun. 2017 Aug 15;8(1):253. doi: 10.1038/s41467-017-00271-7. PMID:28811466[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ Jamsen JA, Beard WA, Pedersen LC, Shock DD, Moon AF, Krahn JM, Bebenek K, Kunkel TA, Wilson SH. Time-lapse crystallography snapshots of a double-strand break repair polymerase in action. Nat Commun. 2017 Aug 15;8(1):253. doi: 10.1038/s41467-017-00271-7. PMID:28811466 doi:http://dx.doi.org/10.1038/s41467-017-00271-7
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