DNA polymerase mu explained

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.

Notes and References

1. Web site: Entrez Gene: POLM polymerase (DNA directed), mu.
2. Daley JM, Laan RL, Suresh A, Wilson TE . DNA joint dependence of pol X family polymerase action in nonhomologous end joining . J. Biol. Chem. . 280 . 32 . 29030–7 . August 2005 . 15964833 . 10.1074/jbc.M505277200 . free .
3. Mahajan KN, Nick McElhinny SA, Mitchell BS, Ramsden DA . 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 . 12077346 . 139779 . 10.1128/MCB.22.14.5194-5202.2002.
4. Nick McElhinny SA, Ramsden DA . 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 . 15242403 . 10.1111/j.0105-2896.2004.00160.x . 36516952 .
5. Nick McElhinny SA, Havener JM, Garcia-Diaz M . 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 . 16061182 . 10.1016/j.molcel.2005.06.012 . etal. free .
6. Bertocci B, De Smet A, Berek C, Weill JC, Reynaud CA . Immunoglobulin kappa light chain gene rearrangement is impaired in mice deficient for DNA polymerase mu . Immunity . 19 . 2 . 203–11 . August 2003 . 12932354 . 10.1016/S1074-7613(03)00203-6. free .
7. Bertocci B, De Smet A, Weill JC, Reynaud CA . 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 . 16860755 . 10.1016/j.immuni.2006.04.013 . free .
8. Lucas D, Escudero B, Ligos JM, Segovia JC, Estrada JC, Terrados G, Blanco L, Samper E, Bernad A . Feb 2009 . Altered hematopoiesis in mice lacking DNA polymerase mu is due to inefficient double-strand break repair . PLOS Genet . 5 . 2. e1000389 . 10.1371/journal.pgen.1000389 . 19229323 . 2638008 . free .