Elsevier

DNA Repair

Volume 6, Issue 4, 1 April 2007, Pages 443-453
DNA Repair

Mammalian single-strand break repair: Mechanisms and links with chromatin

https://doi.org/10.1016/j.dnarep.2006.10.006Get rights and content

Abstract

Thousands of cellular single-strand breaks (SSBs) arise in cells each day, from attack of deoxyribose and DNA bases by reactive oxygen species and other electrophilic molecules, and from the intrinsic instability of DNA. If not repaired, SSBs can disrupt transcription and replication and can be converted into potentially clastogenic and/or lethal DNA double-strand breaks. Here, I present an updated model for the repair of SSBs, and speculate on the possible impact of chromatin structure and remodelling on single-strand break repair (SSBR) processes.

Section snippets

The detection of SSBs

SSBR can be divided into four basic steps, beginning with SSB detection and signaling (Fig. 1A). This appears to be achieved by poly (ADP-ribose) polymerase-1 (PARP-1) and possibly also poly (ADP-ribose) polymerase-2 (PARP-2), which rapidly bind to and are activated by DNA strand breaks ([1], [2], [3], and reviewed in [4]). Once activated, PARP-1 covalently modifies itself and other target proteins with long chains of negatively charged poly ADP-ribose (PAR) [4], [5]. The binding and activity

Replication-coupled SSBR

As discussed above, the XRCC1–Lig3α interaction is partly or largely dispensable for XRCC1-dependent repair of EMS-induced SSBs during S/G2 [100], [101], [102]. Consequently, we have proposed that in addition to the rapid SSBR process(es) that presumably operate throughout interphase, S/G2 phase cells possess an additional, XRCC1-dependent, SSBR process that is intimately linked to DNA replication and which we have termed replication-coupled SSBR (RC-SSBR) [107], [108]. Moreover, the

SSBs and chromatin

Within chromosomes, each 147 base pairs of DNA is wrapped ∼1.6 times around a histone octamer comprised of two molecules each of the histones H2A, H2B, H3, and H4, creating a structure known as the nucleosome. In addition, chromatin is packaged into higher order fibres that further compact DNA. While in recent years there has been an explosion of papers describing the impact of chromatin structure on the detection and repair of UV damage and DNA double-strand breaks, little is known about the

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      The major DNA repair pathways include base excision repair (BER), nucleotide excision repair (NER), single-strand break repair (SSBR) and double-strand break repair (DSBR) [1,2]. BER repairs non-bulky DNA adducts, such as oxidised nucleotides [3], NER repairs bulky, helix distorting DNA adducts [4], SSBR repairs single-strand cuts in the double-helix [5] and DSBR functions via multiple downstream repair pathways, predominantly non-homologous end-joining (NHEJ) and homologous recombination (HR) [6]. Despite these highly complex and efficient repair pathways, DNA repair is imperfect and can therefore lead to the formation of mutations throughout our genomes [7,8].

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