title: Moonlighting at replication forks - a new life for homologous recombination proteins BRCA1, BRCA2 and RAD51.
abstract: Coordination between DNA replication and DNA repair ensures maintenance of genome integrity, which is lost in cancer cells. Emerging evidence has linked homologous recombination (HR) proteins RAD51, BRCA1 and BRCA2 to the stability of nascent DNA. This function appears to be distinct from double-strand break (DSB) repair and is in part due to the prevention of MRE11-mediated degradation of nascent DNA at stalled forks. The role of RAD51 in fork protection resembles the activity described for its prokaryotic orthologue RecA, which prevents nuclease-mediated degradation of DNA and promotes replication fork restart in cells challenged by DNA-damaging agents. Here, we examine the mechanistic aspects of HR-mediated fork protection, addressing the crosstalk between HR and replication proteins.
authors.affiliation: DNA metabolism laboratory, IFOM-The Firc Institute of Molecular Oncology, Milan, Italy.
authors.forename: Arun Mouli
authors.initials: AM
authors.lastname: Kolinjivadi
authors.affiliation: DNA metabolism laboratory, IFOM-The Firc Institute of Molecular Oncology, Milan, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Sannino
authors.affiliation: DNA metabolism laboratory, IFOM-The Firc Institute of Molecular Oncology, Milan, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: de Antoni
authors.affiliation: DNA metabolism laboratory, IFOM-The Firc Institute of Molecular Oncology, Milan, Italy.
authors.forename: Hervé
authors.initials: H
authors.lastname: Técher
authors.affiliation: DNA metabolism laboratory, IFOM-The Firc Institute of Molecular Oncology, Milan, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Baldi
authors.affiliation: DNA metabolism laboratory, IFOM-The Firc Institute of Molecular Oncology, Milan, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Costanzo
mesh_terms: D017766:Acid Anhydride Hydrolases; D000818:Animals; D019313:BRCA1 Protein / Q000378:metabolism*; D024682:BRCA2 Protein / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000378:metabolism; D043171:Chromosomal Instability; D053960:DNA Breaks; D045643:DNA Repair Enzymes / Q000737:chemistry / Q000378:metabolism; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D059765:Homologous Recombination; D006801:Humans; D000076228:MRE11 Homologue Protein; D008954:Models, Biological; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism; D055503:Protein Multimerization; D051135:Rad51 Recombinase / Q000378:metabolism*; D051716:Replication Protein A / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C121766:MRE11 protein, human; C112156:NBN protein, human; D009687:Nuclear Proteins; D051716:Replication Protein A; C495153:RAD51 protein, human; D051135:Rad51 Recombinase; D000076228:MRE11 Homologue Protein; D017766:Acid Anhydride Hydrolases; C112158:RAD50 protein, human; D045643:DNA Repair Enzymes
keywords: DNA recombination; DNA replication; genome stability