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PolD1 Antibody

RRID:AB_2620355

Antibody ID

AB_2620355

Target Antigen

PolD1 human, mouse

Proper Citation

(Thermo Fisher Scientific Cat# A304-007A, RRID:AB_2620355)

Clonality

polyclonal antibody

Reference

PMID:29754823

Comments

Discontinued; Applications: WB (1:1,000-1:5,000), IP (2-10 µg/mg lysate)

Host Organism

rabbit

Vendor

Thermo Fisher Scientific

Cat Num

A304-007A

Publications that use this research resource

Polε Instability Drives Replication Stress, Abnormal Development, and Tumorigenesis.

  • Bellelli R
  • Mol. Cell
  • 2018 May 17

Literature context:


Abstract:

DNA polymerase ε (POLE) is a four-subunit complex and the major leading strand polymerase in eukaryotes. Budding yeast orthologs of POLE3 and POLE4 promote Polε processivity in vitro but are dispensable for viability in vivo. Here, we report that POLE4 deficiency in mice destabilizes the entire Polε complex, leading to embryonic lethality in inbred strains and extensive developmental abnormalities, leukopenia, and tumor predisposition in outbred strains. Comparable phenotypes of growth retardation and immunodeficiency are also observed in human patients harboring destabilizing mutations in POLE1. In both Pole4-/- mouse and POLE1 mutant human cells, Polε hypomorphy is associated with replication stress and p53 activation, which we attribute to inefficient replication origin firing. Strikingly, removing p53 is sufficient to rescue embryonic lethality and all developmental abnormalities in Pole4 null mice. However, Pole4-/-p53+/- mice exhibit accelerated tumorigenesis, revealing an important role for controlled CMG and origin activation in normal development and tumor prevention.

Funding information:
  • NIAID NIH HHS - U01 AI070499(United States)