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(NAS Colloquium) Links Between Recombination and Replication: Vital Roles of Recombination (2002)
Proceedings of the National Academy of Sciences (PNAS)

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Colloquium on Links Between Recombination and Replication: Vital Roles of Recombination

Introduction

Links between recombination and replication: Vital roles of recombination

Charles Radding

Department of Genetics, Yale University, New Haven, CT 06520

There has been a sea change in how we view genetic recombination. When germ cells are produced in higher organisms, genetic recombination assures the proper segregation of like chromosomes. In the course of that process, called meiosis, recombination not only assures segregation of one chromosome of each type to progeny germ cells, but also further shuffles the genetic deck, contributing to the unique inheritance of individuals. In a nutshell, that is the classical view of recombination. We have also known for many years that in bacteria recombination plays a role in horizontal gene transfer and in replication itself, the latter by establishing some of the replication forks that are the structural scaffolds for copying DNA. In recent years, however, we have become increasingly aware that replication, which normally starts without any help from recombination, is a vulnerable process that frequently leads to broken DNA. The enzymes of recombination play a vital role in the repair of those breaks. The recombination enzymes can function via several different pathways that mediate the repair of breaks, as well as restoration of replication forks that are stalled by other kinds of damage to DNA. Thus, to the classical view of recombination as an engine of inheritance we must add the view of recombination as a vital housekeeping function that repairs breaks suffered in the course of replication. We have also known for many years that genomic instability—including mutations, chromosomal rearrangements, and aneuploidy—is a hallmark of cancer cells. Although genomic instability has many contributing causes, including faulty replication, there are many indications that recombination, faulty or not, contributes to genome instability and cancer as well.

The colloquium Links Between Recombination and Replication: Vital Roles of Recombination was convened to broaden awareness of this evolving area of research. Papers generated by this colloquium are published here. To encourage the desired interactions of specialists, we invited some contributions that deal only with recombination or replication in addition to contributions on the central thesis of functional links between recombination and replication. To aid the nonspecialist and specialist alike, we open the set of papers with a historical overview by Michael Cox and we close the set with a commentary on the meeting and the field by Andrei Kuzminov.

The organizing committee consisted of Nicolas Cozzarelli, James Haber, Kenneth Marians, and me. I am grateful to them for valuable advice as well as yeoman’s work in supervising the reviewing and editing of submitted papers. I also wish to acknowledge the invaluable assistance of staff at the National Academy of Sciences.

This paper results from the National Academy of Sciences colloquium, “Links Between Recombination and Replication: Vital Roles of Recombination,” held November 10–12, 2000, in Irvine, CA.

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Front Matter (R1-R3)
Links between recombination and replication: Vital roles of recombination (8172-8172)
Historical overview: Searching for replication help in all of the rec places (8173-8180)
Rescue of arrested replication forks by homologous recombination (8181-8188)
Circles: The replication-recombination-chromosome segregation connection (8189-8195)
Participation of recombination proteins in rescue of arrested replication forks in UV-irradiated Escherichia coli need not involve recombination (8196-8202)
Effects of mutations involving cell division, recombination, and chromosome dimer resolution on a priA2::kan mutant (8203-8210)
RecA protein promotes the regression of stalled replication forks in vitro (8211-8218)
Topological challenges to DNA replication: Conformations at the fork (8219-8226)
Rescue of stalled replication forks by RecG: Simultaneous translocation on the leading and lagging strand templates supports an active DNA unwinding model of fork reversal and Holliday junction formation (8227-8234)
Formation of Holliday junctions by regression of nascent DNA in intermediates containing stalled replication forks: RecG stimulates regression even when the DNA is negatively supercoiled (8235-8240)
Single-strand interruptions in replicating chromosomes cause double-strand breaks (8241-8246)
Handoff from recombinase to replisome: Insights from transportation (8247-8254)
Break-induced replication: A review and an example in budding yeast (8255-8262)
Links between replication and recombination in Saccharomyces cerevisiae: A hypersensitive requirement for homologous recombination in the absence of Rad27 activity (8263-8269)
Evidence that replication fork components catalyze establishment of cohesion between sister chromatids (8270-8275)
Rad52 forms DNA repair and recombination centers during S phase (8276-8282)
A yeast gene, MGS1, encoding a DNA-dependent AAA+ ATPase is required to maintain genome stability (8283-8289)
The tight linkage between DNA replication and double-strand break repair in bacteriophage T4 (8290-8297)
Mediator proteins orchestrate enzyme-ssDNA assembly during T4 recombination-dependent DNA replication and repair (8298-8305)
Two recombination-dependent DNA replication pathways of bacteriophage T4, and their roles in mutagenesis and horizontal gene transfer (8306-8311)
Bacteriophage T4 gene 41 helicase and gene 59 helicase-loading protein: A versatile couple with roles in replication and recombination (8312-8318)
Instability of repetitive DNA sequences: The role of replication in multiple mechanisms (8319-8325)
Repeat expansion by homologous recombination in the mouse germ line at palindromic sequences (8326-8333)
Stationary-phase mutation in the bacterial chromosome: Recombination protein and DNA polymerase IV dependence (8334-8341)
Managing DNA polymerases: Coordinating DNA replication, DNA repair, and DNA recombination (8342-8349)
Roles of DNA polymerases V and II in SOS-induced error-prone and error-free repair in Escherichia coli (8350-8354)
Accuracy of lesion bypass by yeast and human DNA polymerase n (8355-8360)
ATP bound to the orgin recognition complex is important for preRC formation (8361-8367)
Creating a dynamic picture of the sliding clamp during T4 DNA polymerases holoenzyme assembly by using fluorescence resonance energy transfer (8368-8375)
Interaction of the ß sliding clamp with MutS, ligase, and DNA polymerase I (8376-8380)
Defining the roles of individual residues in the single-stranded DNA binding site of PcrA helicase (8381-8387)
Homologous DNA recombination in vertebrate cells (8388-8394)
Meiotic recombination and chromosome segregation in Schizosaccharomyces pombe (8395-8402)
Manipulating the mammalian genome by homologous recombination (8403-8410)
Assembly of RecA-like recombinases: Distinct roles for mediator proteins in mitosis and meiosis (8411-8418)
Domain structure and dynamics in the helical filaments formed by RecA and Rad51 on DNA (8419-8424)
Homologous genetic recombination as an intrinsic dynamic property of a DNA structure induced by RecA/Rad51-family proteins: A possible advantage of DNA over RNA as genomic material (8425-8432)
The synaptic activity of HsDmc1, a human reccombination protein specific to meiosis (8433-8439)
Complex formation by the human RAD51C and XRCC3 recombination repair proteins (8440-8446)
Rad54 protein stimulates the postsynaptic phase of Rad51 protein-mediated DNA strand exchange (8447-8453)
The architecture of the human Rad54-DNA complex provides evidence for protein translocation along DNA (8454-8460)
DNA replication meets genetic exchange: Chromosomal damage and its repair by homologous recombination (8461-8468)
Colloquium Program (8469-8471)