Quality control mechanisms in cellular and systemic DNA damage responses

Article ID	Journal	Published Year	Pages	File Type
10736557	Ageing Research Reviews	2015	9 Pages	PDF

Abstract

The maintenance of the genome is of pivotal importance for the functional integrity of cells and tissues. The gradual accumulation of DNA damage is thought to contribute to the functional decline of tissues and organs with ageing. Defects in multiple genome maintenance systems cause human disorders characterized by cancer susceptibility, developmental failure, and premature ageing. The complex pathological consequences of genome instability are insufficiently explained by cell-autonomous DNA damage responses (DDR) alone. Quality control pathways play an important role in DNA repair and cellular DDR pathways. Recent years have revealed non-cell autonomous effects of DNA damage that impact the physiological adaptations during ageing. We will discuss the role of quality assurance pathways in cell-autonomous and systemic responses to genome instability.

Keywords

ERCC-1 HIF-1 RANKL NHEJ ERK RPA BER RNAPII IGF-1 6-4PPs UPR UBC RAD XPC NBS ARF RADiation sensitive Cul4 Mms2 ICLS DDR DDB2 NF-κB Cullin 4 DSB SIRT6 SASP Ataxia telangiectasia TLS sirtuin 6 PCNA Jnk RNA polymerase II Janus kinase ataxia telangiectasia mutated c-Jun N-terminal kinase COFs cpd NER MAPK Mdm2 xeroderma pigmentosum ROS Adenosine Triphosphate ATP DNA damage STAT Proliferating Cell Nuclear Antigen interleukin DNA repair excision repair cross-complementation group 1 nucleotide excision repair base excision repair replication protein A Tyr Tyrosinase Genome stability ATM cyclobutane pyrimidine dimer Ageing translesion synthesis Nijmegen breakage syndrome Progeroid syndromes Cockayne syndrome Ubiquitin proteasome system extracellular signal regulated kinase DNA double strand break hypoxia inducible factor 1 Insulin like growth factor 1 non-homologous end joining nuclear factor kappa B FoxO Senescence associated secretory phenotype Signal transducer and activator of transcription mouse double minute 2 homolog Homologous recombination ultraviolet light Growth hormone DNA damage response Unfolded protein response mitogen-activated protein kinase mitogen-activated protein kinase 1 JAK Fanconi anaemia Reactive oxygen species receptor activator of nuclear factor kappa B ligand UPS