Coordination of DNA single strand break repair

Abstract

The genetic material of all organisms is susceptible to modification. In some instances, these changes are programmed, such as the formation of DNA double strand breaks during meiotic recombination to generate gamete variety or class switch recombination to create antibody diversity. However, in most cases, genomic damage is potentially harmful to the health of the organism, contributing to disease and aging by promoting deleterious cellular outcomes. A proportion of DNA modifications are caused by exogenous agents, both physical (namely ultraviolet sunlight and ionizing radiation) and chemical (such as benzopyrene, alkylating agents, platinum compounds and psoralens), which can produce numerous forms of DNA damage, including a range of “simple” and helix-distorting base lesions, abasic sites, crosslinks and various types of phosphodiester strand breaks. More significant in terms of frequency are endogenous mechanisms of modification, which include hydrolytic disintegration of DNA chemical bonds, attack by reactive oxygen species and other byproducts of normal cellular metabolism, or incomplete or necessary enzymatic reactions (such as topoisomerases or repair nucleases). Both exogenous and endogenous mechanisms are associated with a high risk of single strand breakage, either produced directly or generated as intermediates of DNA repair. This review will focus upon the creation, consequences and resolution of single strand breaks, with a particular focus on two major coordinating repair proteins: poly(ADP-ribose) polymerase 1 (PARP1) and X-ray repair cross-complementing protein 1 (XRCC1).

Bcl2-Expressing Quiescent Type B Neural Stem Cells in the Ventricular–Subventricular Zone Are Resistant to Concurrent Temozolomide/X-Irradiation

“…In quiescent type B NSCs, repair of double‐strand break defaults to the nonhomologous end joining pathway (NHEJ) . Ionizing radiation also generates large numbers of single‐strand breaks and these are repaired by a base excision repair subpathway . As stated above, Achanta et al reported the loss of type B cells following a single fraction of 10 Gy .…”

Coordination of DNA Base Excision Repair by Protein-Protein Interactions

“…The DNA breaks are detected primarily by poly(ADP-ribose) polymerase 1 (PARP1); the unblocking of 3′-and 5′-ends in breaks is catalyzed by specific activities of APE1, PNKP, aprataxin (APTX), and tyrosyl-DNA phosphodiesterase 1 (TDP1); gap filling and ligation are catalyzed by the same set of enzymes that participate in the respective steps of the short-patch repair of the damaged DNA bases (Polβ and LigIIIα). PARP1 is activated via the interaction with the damaged DNA; it catalyzes the synthesis of poly(ADP-ribose) (PAR) and covalent attachment of the PAR polymer to PARP1 itself and other proteins involved in the DNA repair [4,5]. The XRCC1 protein is considered to be a main target of PARP1 catalyzed poly(ADP-ribosyl)ation.…”

“…The XRCC1 protein is considered to be a main target of PARP1 catalyzed poly(ADP-ribosyl)ation. PARP1 has been suggested to play the main role in recruitment of the XRCC1 protein to the damages of chromosomal DNA [4,5]. XRCC1 displays no enzymatic activity and is proposed to function as a scaffold protein of the BER process.…”

“…Base excision repair (BER), which ensures correction of the most abundant damages-modified nitrogenous bases and apurinic/apyrimidinic (AP) sites-is critically important for survival of human cells [1][2][3]. Enzyme and protein factors of BER also participate in the repair of DNA single-strand breaks (SSBs) considered as a separate pathway of the BER system [4,5]. The other repair systems (Figure 1) deal with bulky nucleobase lesions (NER), DNA double-strand breaks (HR; NHEJ), and mismatched bases (MMR).…”

Role of oxidation of XRCC1 protein in regulation of mammalian DNA repair process

“…Эксцизионная репарация оснований (BER) обеспечивает коррекцию самых многочисленных повреждений ДНК -модифицированных оснований, апуриновых/апиримидиновых (АР) сайтов и одноцепочечных разрывов [1], возникающих под воздействием различных факторов, включая активные формы кислорода. Активность ферментов, катализирующих отдельные стадии многоступенчатого процесса BER, координируется с участием поли(АДФ-рибоза) полимераз (PARP1 и PARP2) и белка XRCC1 (X-ray repair cross-complementing protein 1), опосредующих сборку мультибелковых ансамблей (репарасом).…”