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Human DNA Polymerase β’s endonuclease activity prevents mitotic chromosome instability (LB119)
Author(s) -
Carron Emily,
Chen Desheng,
Makridakis Nick
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.lb119
Subject(s) - anaphase , chromosome instability , mitosis , metaphase , dna polymerase , microbiology and biotechnology , biology , endonuclease , chromosome segregation , centromere , polymerase , genetics , chromosome , cell cycle , dna , cell , gene
Most tumors have numerical and structural chromosome aberrations that can provide selective growth advantages. It has been reported that overexpression of DNA Polymerase B (Pol β) contributes to chromosome instability by inducing aneuplody, telomere fusions, and a deficient mitotic checkpoint. However, the mechanism is currently unknown. Here, we report that Pol β’s endonuclease activity plays an important role in maintaining chromosome stability by collaborating with Topoisomerase IIα. Our results indicate that Pol β has endonuclease activity, and that this activity is required to prevent chromosomal instability during mitosis as deletion of Pol β induces aneuploidy, the formation of anaphase bridges and micronuclei. Moreover, cells expressing the endonuclease deficient E216K mutant accumulate more anaphase bridges and micronuclei than those expressing wild‐type Pol β. Consistent with these observations, Pol β localizes near the centromere in metaphase. This data suggests that Pol β’s endonuclease activity plays a role in mitotic chromosome segregation. Grant Funding Source : DOD grant PC094628, and NIH grant 8 P20 GM103518 (to NM