Biology:DNA polymerase mu
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DNA polymerase mu is a polymerase enzyme found in eukaryotes. In humans, this protein is encoded by the POLM gene.[1]
Function
Pol μ is a member of the X family of DNA polymerases. It participates in resynthesis of damaged or missing nucleotides during the non-homologous end joining (NHEJ) pathway of DNA repair.[2] Pol μ interacts with Ku and DNA ligase IV, which also participate in NHEJ.[3] It is structurally and functionally related to pol λ, and, like pol λ, pol μ has a BRCT domain that is thought to mediate interactions with other DNA repair proteins.[4] Unlike pol λ, however, pol μ has the unique ability to add a base to a blunt end that is templated by the overhang on the opposite end of the double-strand break.[5] Pol μ is also closely related to terminal deoxynucleotidyl transferase (TdT), a specialized DNA polymerase that adds random nucleotides to DNA ends during V(D)J recombination, the process by which B-cell and T-cell receptor diversity is generated in the vertebrate immune system. Like TdT, pol μ participates in V(D)J recombination, but only during light chain rearrangements.[6] This is distinct from pol λ, which is involved in heavy chain rearrangements.[7]
POLM mutant mice
In polymerase mu mutant mice, hematopoietic cell development is defective in several peripheral and bone marrow cell populations with about a 40% decrease in bone marrow cell number that includes several hematopoietic lineages.[8] Expansion potential of hematopoietic progenitor cells is also reduced. These characteristics correlate with reduced ability to repair double-strand breaks in hematopoietic tissue. Whole body gamma irradiation of polymerase mu mutant mice indicates that polymerase mu also has a role in double-strand break repair in other tissues unrelated to hematopoietic tissue. Thus polymerase mu has a significant role in maintaining genetic stability in hematopoietic and non-hematopoietic tissue.
References
- ↑ "Entrez Gene: POLM polymerase (DNA directed), mu". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=27434.
- ↑ "DNA joint dependence of pol X family polymerase action in nonhomologous end joining". J. Biol. Chem. 280 (32): 29030–7. August 2005. doi:10.1074/jbc.M505277200. PMID 15964833.
- ↑ "Association of DNA polymerase mu (pol mu) with Ku and ligase IV: role for pol mu in end-joining double-strand break repair". Mol. Cell. Biol. 22 (14): 5194–202. July 2002. doi:10.1128/MCB.22.14.5194-5202.2002. PMID 12077346.
- ↑ "Sibling rivalry: competition between Pol X family members in V(D)J recombination and general double strand break repair". Immunol. Rev. 200: 156–64. August 2004. doi:10.1111/j.0105-2896.2004.00160.x. PMID 15242403.
- ↑ "A gradient of template dependence defines distinct biological roles for family X polymerases in nonhomologous end joining". Mol. Cell 19 (3): 357–66. August 2005. doi:10.1016/j.molcel.2005.06.012. PMID 16061182.
- ↑ "Immunoglobulin kappa light chain gene rearrangement is impaired in mice deficient for DNA polymerase mu". Immunity 19 (2): 203–11. August 2003. doi:10.1016/S1074-7613(03)00203-6. PMID 12932354.
- ↑ "Nonoverlapping functions of DNA polymerases mu, lambda, and terminal deoxynucleotidyltransferase during immunoglobulin V(D)J recombination in vivo". Immunity 25 (1): 31–41. July 2006. doi:10.1016/j.immuni.2006.04.013. PMID 16860755. http://www.hal.inserm.fr/docs/00/31/95/59/PDF/Table_3.pdf.
- ↑ "Altered hematopoiesis in mice lacking DNA polymerase mu is due to inefficient double-strand break repair". PLOS Genet 5 (2): e1000389. Feb 2009. doi:10.1371/journal.pgen.1000389. PMID 19229323.
External links
- Overview of all the structural information available in the PDB for UniProt: Q9NP87 (Human DNA-directed DNA/RNA polymerase mu) at the PDBe-KB.
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