(Single-stranded DNA) gaps in understanding BRCAness

Trends in Genetics, vol. 40, pp. 757–771

Abstract

The tumour-suppressive roles of BRCA1 and 2 have been attributed to three seemingly distinct functions - homologous recombination, replication fork protection, and single-stranded (ss)DNA gap suppression - and their relative importance is under debate. In this review, we examine the origin and resolution of ssDNA gaps and discuss the recent advances in understanding the role of BRCA1/2 in gap suppression. There are ample data showing that gap accumulation in BRCA1/2-deficient cells is linked to genomic instability and chemosensitivity. However, it remains unclear whether there is a causative role and the function of BRCA1/2 in gap suppression cannot unambiguously be dissected from their other functions. We therefore conclude that the three functions of BRCA1 and 2 are closely intertwined and not mutually exclusive.

Authors 4

1. Anne Schreuder Aachen Department of Human Genetics

   Leiden University Medical Center · Oncode Institute

   Affiliation as printed

   Leiden University Medical Center, Department of Human Genetics, Leiden, The Netherlands; Oncode Institute, Utrecht, The Netherlands

   Leiden University Medical Center, Department of Human Genetics, Leiden, The Netherlands

   Oncode Institute, Utrecht, The Netherlands

2. Tiemen J. Wendel Aachen Department of Human Genetics

   Leiden University Medical Center · Oncode Institute

   Affiliation as printed

   Leiden University Medical Center, Department of Human Genetics, Leiden, The Netherlands; Oncode Institute, Utrecht, The Netherlands

   Leiden University Medical Center, Department of Human Genetics, Leiden, The Netherlands

   Oncode Institute, Utrecht, The Netherlands

3. Carlo G.V. Dorresteijn Aachen Department of Human Genetics

   Leiden University Medical Center

   Affiliation as printed

   Leiden University Medical Center, Department of Human Genetics, Leiden, The Netherlands

4. Sylvie M. Noordermeer corresponding Aachen Department of Human Genetics

   Leiden University Medical Center · Oncode Institute

   Affiliation as printed

   Leiden University Medical Center, Department of Human Genetics, Leiden, The Netherlands; Oncode Institute, Utrecht, The Netherlands. Electronic address: s.m.noordermeer@lumc.nl

   Leiden University Medical Center, Department of Human Genetics, Leiden, The Netherlands

   Oncode Institute, Utrecht, The Netherlands