title: New factors in mammalian DNA repair-the chromatin connection.
abstract: In response to DNA damage mammalian cells activate a complex network of stress response pathways collectively termed DNA damage response (DDR). DDR involves a temporary arrest of the cell cycle to allow for the repair of the damage. DDR also attenuates gene expression by silencing global transcription and translation. Main function of DDR is, however, to prevent the fixation of debilitating changes to DNA by activation of various DNA repair pathways. Proper execution of DDR requires careful coordination between these interdependent cellular responses. Deregulation of some aspects of DDR orchestration is potentially pathological and could lead to various undesired outcomes such as DNA translocations, cellular transformation or acute cell death. It is thus critical to understand the regulation of DDR in cells especially in the light of a strong linkage between the DDR impairment and the occurrence of common human diseases such as cancer. In this review we focus on recent advances in understanding of mammalian DNA repair regulation and a on the function of PAXX/c9orf142 and ZNF281 proteins that recently had been discovered to play a role in that process. We focus on regulation of double-strand DNA break (DSB) repair via the non-homologous end joining pathway, as unrepaired DSBs are the primary cause of pathological cellular states after DNA damage. Interestingly these new factors operate at the level of chromatin, which reinforces a notion of a central role of chromatin structure in the regulation of cellular DDR regulation.
authors.affiliation: ENEA Research Center Casaccia, Laboratory of Biosafety and Risk Assessment, Rome, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Raschellà
authors.affiliation: Department of Experimental Medicine &Surgery, University of Rome Tor Vergata, Rome, Italy.|MRC Toxicology Unit, Hodgkin Building, Leicester, UK.
authors.forename: G
authors.initials: G
authors.lastname: Melino
authors.affiliation: MRC Toxicology Unit, Hodgkin Building, Leicester, UK.
authors.forename: M
authors.initials: M
authors.lastname: Malewicz
mesh_terms: D000818:Animals; D002453:Cell Cycle; D002843:Chromatin / Q000378:metabolism*; D053903:DNA Breaks, Double-Stranded; D059766:DNA End-Joining Repair / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D012097:Repressor Proteins; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016335:Zinc Fingers
chemical_list: D002843:Chromatin; D004268:DNA-Binding Proteins; C000595075:PAXX protein, human; D012097:Repressor Proteins; D015534:Trans-Activators; C120370:ZNF281 protein, human