Division of labor: DNA repair and the cell cycle specific functions of the Mre11 complex Journal Article

Authors: Adelman, C. A.; Petrini, J. H. J.
Article Title: Division of labor: DNA repair and the cell cycle specific functions of the Mre11 complex
Abstract: Genomic integrity is maintained via the concerted action of proteins that coordinate and control DNA replication and those that respond to DNA damage. The Mre11 complex is a mediator of the DNA damage response through its functions in DNA double strand break (DSB) sensing, checkpoint activation and recombinational DNA repair. The complex responds to mitotic and meiotic DSBs, and is also activated in cells experiencing DNA replication stress. The Mre11 complex's role in recombinational repair primarily concerns the promotion of homologous recombination (HR), but it is also implicated in non-homologous end joining (NHEJ) - a DSB repair mechanism prevalent in non-dividing cells. We recently characterized deletion of the Mre11 complex member, Rad50, in a number of postmitotic and proliferative tissues of the mouse. These studies indicated that the complex is dispensable in postmitotic tissues, but loss of Rad50 in proliferating cells resulted in accumulation of unrepaired, DNA replication-dependent lesions. The data suggest that the Mre11 complex is not a major contributor to NHEJ and support the interpretation that its role in recombinational DNA repair is largely restricted to dividing cells, in which repair involving sister chromatids predominates. An exception to this concept is manifest in previous work from our laboratory revealing that the mammalian Mre11 complex promotes meiotic DSB repair, an event involving recombination between sister chromatids of homologous chromosomes and taking place in cells not undergoing replication. Together these studies highlight the importance of cell cycle and cell type specific modulation of the Mre11 complex's repair activities in vivo. ©2009 Landes Bioscience.
Keywords: review; nonhuman; dna replication; protein function; cell proliferation; mitosis; telomere; meiosis; mammalia; mre11 protein; rad50 protein; cell viability; cell cycle; dsb repair; mre11; nbs1; postmitotic; rad50; cell compartmentalization; cell cycle progression; cell cycle s phase; cell division; cell function; complex formation; dna repair; sister chromatid; somatic cell
Journal Title: Cell Cycle
Volume: 8
Issue: 10
ISSN: 1538-4101
Publisher: Taylor & Francis Inc.  
Date Published: 2009-05-15
Start Page: 1510
End Page: 1514
Language: English
PROVIDER: scopus
PUBMED: 19395852
PMCID: PMC3059805
Notes: --- - "Export Date: 30 November 2010" - "Source: Scopus"