Human DNA Polymerase β’s endonuclease activity prevents mitotic chromosome instability (LB119)
Abstract
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Apr 01, 2014
- Source ID
- 10.1096/fasebj.28.1_supplement.lb119
Entities
People
- Desheng Chen
- Emily Carron
- Nick Makridakis
Organizations
- Baylor College of Medicine
- National Institutes of Health
- Tulane University of Louisiana
- United States Department of Defense