“DNA polymerase mu”的意思、由来-开放百科全书

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 heavy chain rearrangements.^[6] This is distinct from pol λ, which is involved in light 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

1. ^{{cite web | title = Entrez Gene: POLM polymerase (DNA directed), mu| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=27434| accessdate = }}
2. ^{{cite journal |vauthors=Daley JM, Laan RL, Suresh A, Wilson TE |title=DNA joint dependence of pol X family polymerase action in nonhomologous end joining |journal=J. Biol. Chem. |volume=280 |issue=32 |pages=29030–7 |date=August 2005 |pmid=15964833 |doi=10.1074/jbc.M505277200 |url=}}
3. ^{{cite journal |vauthors=Mahajan KN, Nick McElhinny SA, Mitchell BS, Ramsden DA |title=Association of DNA polymerase mu (pol mu) with Ku and ligase IV: role for pol mu in end-joining double-strand break repair |journal=Mol. Cell. Biol. |volume=22 |issue=14 |pages=5194–202 |date=July 2002 |pmid=12077346 |pmc=139779 |doi= 10.1128/MCB.22.14.5194-5202.2002|url=}}
4. ^{{cite journal |vauthors=Nick McElhinny SA, Ramsden DA |title=Sibling rivalry: competition between Pol X family members in V(D)J recombination and general double strand break repair |journal=Immunol. Rev. |volume=200 |issue= |pages=156–64 |date=August 2004 |pmid=15242403 |doi=10.1111/j.0105-2896.2004.00160.x |url=}}
5. ^{{cite journal |vauthors=Nick McElhinny SA, Havener JM, Garcia-Diaz M |title=A gradient of template dependence defines distinct biological roles for family X polymerases in nonhomologous end joining |journal=Mol. Cell |volume=19 |issue=3 |pages=357–66 |date=August 2005 |pmid=16061182 |doi=10.1016/j.molcel.2005.06.012 |url=|display-authors=etal}}
6. ^{{cite journal |vauthors=Bertocci B, De Smet A, Berek C, Weill JC, Reynaud CA |title=Immunoglobulin kappa light chain gene rearrangement is impaired in mice deficient for DNA polymerase mu |journal=Immunity |volume=19 |issue=2 |pages=203–11 |date=August 2003 |pmid=12932354 |doi= 10.1016/S1074-7613(03)00203-6|url=}}
7. ^{{cite journal |vauthors=Bertocci B, De Smet A, Weill JC, Reynaud CA |title=Nonoverlapping functions of DNA polymerases mu, lambda, and terminal deoxynucleotidyltransferase during immunoglobulin V(D)J recombination in vivo |journal=Immunity |volume=25 |issue=1 |pages=31–41 |date=July 2006 |pmid=16860755 |doi=10.1016/j.immuni.2006.04.013 |url=}}
8. ^Lucas D, Escudero B, Ligos JM, Segovia JC, Estrada JC, Terrados G, Blanco L, Samper E, Bernad A. Altered hematopoiesis in mice lacking DNA polymerase mu is due to inefficient double-strand break repair. PLoS Genet. 2009 Feb;5(2):e1000389. doi: 10.1371/journal.pgen.1000389. {{PMID|19229323}}

Function

POLM mutant mice

References