Journal
MOLECULAR AND CELLULAR BIOLOGY
Volume 34, Issue 10, Pages 1733-1746Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/MCB.01345-13
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Funding
- Deutsche Forschungsgemeinschaft [HE 2484/3-1]
- German Ministry for Education and Research (Bundesministerium fur Bildung und Forschung [BMBF]) [0315581]
- The Brain Tumour Charity [8/47] Funding Source: researchfish
- Worldwide Cancer Research [13-1083] Funding Source: researchfish
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The PML tumor suppressor has been functionally implicated in DNA damage response and cellular senescence. Direct evidence for such a role based on PML knockdown or knockout approaches is still lacking. We have therefore analyzed the irradiation-induced DNA damage response and cellular senescence in human and mouse fibroblasts lacking PML. Our data show that PML nuclear bodies (NBs) nonrandomly associate with persistent DNA damage foci in unperturbed human skin and in high-dose-irradiated cell culture systems. PML bodies do not associate with transient gamma H2AX foci after low-dose gamma irradiation. Super-resolution microscopy reveals that all PML bodies within a nucleus are engaged at Rad51- and RPA-containing repair foci during ongoing DNA repair. The lack of PML (i) does not majorly affect the DNA damage response, (ii) does not alter the efficiency of senescence induction after DNA damage, and (iii) does not affect the proliferative potential of primary mouse embryonic fibroblasts during serial passaging. Thus, while PML NBs specifically accumulate at Rad51/RPA-containing lesions and senescence-derived persistent DNA damage foci, they are not essential for DNA damage-induced and replicative senescence of human and murine fibroblasts.
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