Overview for the histone codes for DNA repair

Abstract

DNA damage occurs continuously as a result of various factors-intracellular metabolism, replication, and exposure to genotoxic agents, such as ionizing radiation and chemotherapy. If left unrepaired, this damage could result in changes or mutations within the cell genomic material. There are a number of different pathways that the cell can utilize to repair these DNA breaks. However, it is of utmost interest to know how the DNA damage is signaled to the various DNA pathways. As DNA damage occurs within the chromatin, we postulate that modifications of histones are important for signaling the position of DNA damage, recruiting the DNA repair proteins to the site of damage, and creating an open structure such that the repair proteins can access the site of damage. We discuss the modifications that occur on the histones and the manner in which they relate to the type of damage that has occurred as well as the DNA repair pathways that are activated.

Fig. 1

(1) DNA bound to chromatin tightly compacted and maintained by Hp1 and KAP-1. (2) DSB occurs and MRN is recruited to DSB displacing Hp1 and KAP-1, revealing H3K9me3. (3) Tip60 and ATM are recruited to H3K9me3. Tip60 acetylates and activates ATM. ATM induces γ-H2AX and autophosphorylates. (4) MDC1 is recruited to γ-H2AX, ATM is activated and extends γ-H2AX, Tip60 acetylates H3/4. (5) MDC1 expands and binds to γ-H2AX which recruits a plethora of repair factors in conjunction with acetylated and methylated histones. Multiple steps are then ready to proceed, including HRR end resection, chromatin remodeling and the rest of the HRR mechanism.