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.

Moonlighting at replication forks - a new life for homologous recombination proteins BRCA1, BRCA2 and RAD51 / A.M. Kolinjivadi, V. Sannino, A. de Antoni, H. Técher, G. Baldi, V. Costanzo. - In: FEBS LETTERS. - ISSN 0014-5793. - 591:8(2017), pp. 1083-1100. [10.1002/1873-3468.12556]

Moonlighting at replication forks - a new life for homologous recombination proteins BRCA1, BRCA2 and RAD51

G. Baldi
Penultimo
Investigation
;
V. Costanzo
Ultimo
Supervision
2017

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.
DNA recombination; DNA replication; genome stability; Animals; BRCA1 Protein; BRCA2 Protein; Cell Cycle Proteins; Chromosomal Instability; DNA Breaks; DNA Repair Enzymes; DNA-Binding Proteins; Humans; MRE11 Homologue Protein; Nuclear Proteins; Protein Multimerization; Rad51 Recombinase; Replication Protein A; DNA Replication; Homologous Recombination; Models, Biological
Settore MED/04 - Patologia Generale
2017
Article (author)
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/577850
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