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DNA-PK Antibody

RRID:AB_10692482

Antibody ID

AB_10692482

Target Antigen

DNA-PK human

Proper Citation

(Cell Signaling Technology Cat# 4602, RRID:AB_10692482)

Clonality

polyclonal antibody

Reference

PMID:29478807

Comments

Applications: W. Consolidation on 11/2018: AB_10692482, AB_10829765, AB_2172709.

Host Organism

rabbit

Vendor

Cell Signaling Technology

Cat Num

4602

Publications that use this research resource

The Histone Chaperones ASF1 and CAF-1 Promote MMS22L-TONSL-Mediated Rad51 Loading onto ssDNA during Homologous Recombination in Human Cells.

  • Huang TH
  • Mol. Cell
  • 2018 Mar 1

Literature context:


Abstract:

The access-repair-restore model for the role of chromatin in DNA repair infers that chromatin is a mere obstacle to DNA repair. However, here we show that blocking chromatin assembly, via knockdown of the histone chaperones ASF1 or CAF-1 or a mutation that prevents ASF1A binding to histones, hinders Rad51 loading onto ssDNA during homologous recombination. This is a consequence of reduced recruitment of the Rad51 loader MMS22L-TONSL to ssDNA, resulting in persistent RPA foci, extensive DNA end resection, persistent activation of the ATR-Chk1 pathway, and cell cycle arrest. In agreement, histones occupy ssDNA during DNA repair in yeast. We also uncovered DNA-PKcs-dependent DNA damage-induced ASF1A phosphorylation, which enhances chromatin assembly, promoting MMS22L-TONSL recruitment and, hence, Rad51 loading. We propose that transient assembly of newly synthesized histones onto ssDNA serves to recruit MMS22L-TONSL to efficiently form the Rad51 nucleofilament for strand invasion, suggesting an active role of chromatin assembly in homologous recombination.

Funding information:
  • Intramural NIH HHS - (United States)
  • NCI NIH HHS - R01 CA095641()