Chromatin disassembly and reassembly during DNA repair

Abstract

Current research is demonstrating that the packaging of the eukaryotic genome together with histone proteins into chromatin is playing a fundamental role in DNA repair and the maintenance of genomic integrity. As is well established to be the case for transcription, the chromatin structure dynamically changes during DNA repair. Recent studies indicate that the complete removal of histones from DNA and their subsequent reassembly onto DNA accompanies DNA repair. This review will present evidence indicating that chromatin disassembly and reassembly occur during DNA repair and that these are critical processes for cell survival after DNA repair. Concomitantly, candidate proteins utilized for these processes will be highlighted.

Chromatin dynamics coupled to DNA repair

“…17,133 Even though post-repair chromatin reassembly occurs mostly with new histones, a portion of the old evicted histones could be recycled and in such a case, Asf1 could exercise the storage function of evicted histones, given its known role in chromatin disassembly. 136 In this context, it has been suggested that Asf1 has a role in chromatin disassembly during DNA repair. 136 Consistent with the idea of the existence of specific mechanisms for restoring epigenetic marks, DNA methyltransferase DNMT1 is recruited to DNA repair sites through its interaction with PCNA.…”

“…136 In this context, it has been suggested that Asf1 has a role in chromatin disassembly during DNA repair. 136 Consistent with the idea of the existence of specific mechanisms for restoring epigenetic marks, DNA methyltransferase DNMT1 is recruited to DNA repair sites through its interaction with PCNA. 145 DNMT1 may preserve cytosine methylation patterns in the newly synthesized DNA, and so participates in the conservation of epigenetic information after repair of DNA damage.…”

“…Such studies have implicated both chromatin assembly factor 1 (CAF-1) and anti-silencing factor 1 (Asf1) in chromatin assembly following the repair of different DNA lesions. 136 Although to differing degrees, inactivation of CAF-1 and Asf1 confers sensitivity to different DNA-damaging agents, such as UV and gamma radiation, radiomimetics and alkylating compounds. 92,136 Through interaction with the sliding clamp protein, PCNA, CAF-1 is recruited to UV-damaged sites where it deposits new histone H3.1 (the major H3 variant, incorporated into chromatin mainly during replication) in a postrepair stage.…”

“…136 Although to differing degrees, inactivation of CAF-1 and Asf1 confers sensitivity to different DNA-damaging agents, such as UV and gamma radiation, radiomimetics and alkylating compounds. 92,136 Through interaction with the sliding clamp protein, PCNA, CAF-1 is recruited to UV-damaged sites where it deposits new histone H3.1 (the major H3 variant, incorporated into chromatin mainly during replication) in a postrepair stage. 133 CAF-1 is also found at DSB sites, 137 where it may also promote incorporation of new histone H3.…”

“…136,142 This functional connection may be mediated by the physical interaction between them 142 and could be the means by which Asf1 is recruited to the DNA damage sites. Asf1 also has the essential function of acting as protein cofactor in the acetylation of non-chromatin histone H3 at lysine 56.…”