RecQ helicases queuing with Srs2 to disrupt Rad51 filaments and suppress recombination (original) (raw)

  1. Dana Branzei2 and
  2. Marco Foiani1
  3. Fondazione Italiana Ricerca sul Cancro (FIRC) Institute of Molecular Oncology Foundation, 20139 Milan, Italy; Dipartimento di Scienze Biomolecolari e Biotecnologie, Università degli Studi di Milano, 20133 Milan, Italy

Homologous recombination (HR) is an important mechanism for the maintenance of genome integrity. HR functions to repair double-strand breaks (DSBs) and single-strand gaps formed during replication or created by DNA damaging agents or from processing DNA lesions. In addition, HR is implicated in the restart of damaged replication forks and functions in telomere length maintenance in cells lacking telomerase. Increasing evidence suggests that HR plays an important role in cancer prevention (Thompson and Schild 2002; Sung and Klein 2006). However, recombination can also be harmful and have oncogenic and mutagenic consequences. It is known that inappropriate or untimely recombination can generate damaging genome rearrangements, such as somatic loss of heterozygosity (LOH), chromosome deletions, inversions, or translocations. Therefore, cells have evolved specific mechanisms to control recombination and to coordinate HR with other responses to DNA damage as well as with replication and progression through the cell cycle. Indeed, several cancer-prone genetic diseases, including the ones caused by mutations in human RecQ helicases, are associated with HR dysfunction. In this issue of Genes & Development, two studies by Bugreev et al. (2007b) and Hu et al. (2007) demonstrate a novel function for two human RecQ helicases, BLM and RECQL5, in regulating an early step of HR, which is related to their role in protecting genome stability.

An important early step of all HR reactions is to use a Rad51 presynaptic filament on single-stranded DNA (ssDNA) (Fig. 1A) to invade a homologous duplex, giving rise to a three-stranded structure called a D-loop (Fig. 1B). HR can then bifurcate into two main subpathways called DSB repair (DSBR) and synthesis-dependent strand annealing (SDSA) (Fig. 2; Allers and Lichten 2001; Hunter and Kleckner 2001). In DSBR, the second DSB end can be captured to form an intermediate with two Holliday junctions (HJs), …