Rad54 functions as a heteroduplex DNA pump modulated by its DNA substrates and Rad51 during D loop formation.

Abstract:

:The displacement loop (D loop) is the product of homology search and DNA strand invasion, constituting a central intermediate in homologous recombination (HR). In eukaryotes, the Rad51 DNA strand exchange protein is assisted in D loop formation by the Rad54 motor protein. Curiously, Rad54 also disrupts D loops. How these opposing activities are coordinated toward productive recombination is unknown. Moreover, a seemingly disparate function of Rad54 is removal of Rad51 from heteroduplex DNA (hDNA) to allow HR-associated DNA synthesis. Here, we uncover features of D loop formation/dissociation dynamics, employing Rad51 filaments formed on ssDNAs that mimic the physiological length and structure of in vivo substrates. The Rad54 motor is activated by Rad51 bound to synapsed DNAs and guided by a ssDNA-binding domain. We present a unified model wherein Rad54 acts as an hDNA pump that drives D loop formation while simultaneously removing Rad51 from hDNA, consolidating both ATP-dependent activities of Rad54 into a single mechanistic step.

journal_name

Mol Cell

journal_title

Molecular cell

authors

Wright WD,Heyer WD

doi

10.1016/j.molcel.2013.12.027

subject

Has Abstract

pub_date

2014-02-06 00:00:00

pages

420-32

issue

3

eissn

1097-2765

issn

1097-4164

pii

S1097-2765(14)00033-1

journal_volume

53

pub_type

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