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
[edit | edit source]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
[edit | edit source]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
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External links
[edit | edit source]- Overview of all the structural information available in the PDB for UniProt: Q9NP87 (Human DNA-directed DNA/RNA polymerase mu) at the PDBe-KB.
