Recombination proteins and rescue of arrested replication forks

Defining replication origin efficiency using DNA fiber assays

“…Cells have evolved efficient fork repair mechanisms to restart stalled forks. These mechanisms are particularly active in prokaryotes, which rely on a single pair of replication forks to duplicate their genome (Michel et al 2007). In contrast, eukaryotes have adopted a different strategy to deal with replication stress, which is based on origin redundancy rather than fork restart at any cost.…”

Regression of Replication Forks Stalled by Leading-strand Template Damage

“…Subsequent studies by many laboratories have elaborated the genetic pathways involved in the processing and repair of stalled replication forks (for reviews, see Refs. [5][6][7][8][9][10][11]. A central feature of many of the models described is one in which the nascent strands at the stalled fork have been unwound from the respective parental template strand and paired together.…”

“…In a topologically constrained molecule, positive supercoiling will provide a strong driving force for spontaneous RFR (14,15). With respect to rescue of the stalled fork (5)(6)(7)(8)(9)(10)(11), the HJ formed can be cleaved by the HJ resolvase, RuvC (16), resulting in rescue of replication by homologous recombination-directed DNA replication, whereby a recombinant joint molecule is formed between the two sister chromosomes, and the replisome is reloaded by a PriA-directed pathway downstream of the damage. In cases where the 5Ј-end of the last Okazaki fragment is further downstream than the 3Ј-end of a stalled nascent leading strand, a template strand switch can occur in the regressed intermediate, extending the nascent leading strand, which, upon resetting of the fork back to its original position, will result in bypass of the lesion.…”

RecFOR Proteins Target RecA Protein to a DNA Gap with Either DNA or RNA at the 5′ Terminus

“…Just one DNA break or replication-blocking lesion is highly toxic to the organism: such damage can block cell division and, in the case of multicellular Eukarya, may lead to cancer (2). In Escherichia coli, several pathways are responsible for the repair of such DNA lesions (3). These pathways include nucleotide or base excision repair, homologous recombinational repair, and lesion bypass.…”

“…Single-stranded DNA (ssDNA) 3 gaps in double-stranded DNA (dsDNA) are one type of damaged DNA. Such gapped DNA (gDNA) can be produced when DNA synthesis stops at a DNA lesion during DNA replication (1).…”