6p1m

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Binary complex of human DNA Polymerase Mu with 1-nt gapped substrate containing template 8OGBinary complex of human DNA Polymerase Mu with 1-nt gapped substrate containing template 8OG

Structural highlights

6p1m is a 4 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 1.65Å
Ligands:, , , , ,
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 double-strand breaks (DSBs) resulting from reactive oxygen species generated by exposure to UV and ionizing radiation are characterized by clusters of lesions near break sites. Such complex DSBs are repaired slowly, and their persistence can have severe consequences for human health. We have therefore probed DNA break repair containing a template 8-oxo-7,8-dihydro-2'-guanosine (8OG) by Family X Polymerase mu (Pol mu) in steady-state kinetics and cell-based assays. Pol mu tolerates 8OG-containing template DNA substrates, and the filled products can be subsequently ligated by DNA Ligase IV during Nonhomologous end-joining. Furthermore, Pol mu exhibits a strong preference for mutagenic bypass of 8OG by insertion of adenine. Crystal structures reveal that the template 8OG is accommodated in the Pol mu active site with none of the DNA substrate distortions observed for Family X siblings Pols beta or lambda. Kinetic characterization of template 8OG bypass indicates that Pol mu inserts adenosine nucleotides with weak sugar selectivity and, given the high cellular concentration of ATP, likely performs its role in repair of complex 8OG-containing DSBs using ribonucleotides.

Unexpected behavior of DNA polymerase Mu opposite template 8-oxo-7,8-dihydro-2'-guanosine.,Kaminski AM, Chiruvella KK, Ramsden DA, Kunkel TA, Bebenek K, Pedersen LC Nucleic Acids Res. 2019 Sep 26;47(17):9410-9422. doi: 10.1093/nar/gkz680. PMID:31435651[5]

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

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. ↑ Kaminski AM, Chiruvella KK, Ramsden DA, Kunkel TA, Bebenek K, Pedersen LC. Unexpected behavior of DNA polymerase Mu opposite template 8-oxo-7,8-dihydro-2'-guanosine. Nucleic Acids Res. 2019 Sep 26;47(17):9410-9422. doi: 10.1093/nar/gkz680. PMID:31435651 doi:http://dx.doi.org/10.1093/nar/gkz680

6p1m, resolution 1.65Å

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