Abstract
The repair of endogenously induced DNA damage is essential to maintain genomic integrity. It has been shown that XRCC1 and PARP1 are involved in the repair of base lesions and SSBs, although the exact mode of action has yet to be determined. Here we show that XRCC1 is involved in the repair of base lesions and SSBs independent of the cell cycle. However, the rate of repair of damage requiring XRCC1 does reflect the damage complexity. The repair of induced DNA damage occurs by PARP1-dependent and PARP1-independent sub-pathways of BER. It is suggested that the repair of SSBs and purine base damage is by a sub-pathway of BER that requires both XRCC1 and PARP1. Repair of pyrimidine base damage may require XRCC1 but does not require PARP1 activity. Therefore, although BER of simple lesions occurs rapidly, pathway choice and the involvement of PARP1 are highly dependent on the types of lesion induced.
Highlights
Cellular metabolism produces a number of reactive oxygen species (ROS) that can be neutralized by superoxide dismutase, catalases and glutathione peroxidases [1]
X-ray cross complementing protein 1 (XRCC1) is a key protein involved in Base excision repair (BER) and is recruited early during BER/single strand break repair (SSBR) to act as a scaffold for the recruitment of numerous BER proteins including AP endonuclease 1 (APE1), Pol , polynucleotide kinase 3’ phosphatase and ligase III [23]
We present the first evidence on the dynamics of recruitment and loss of XRCC1, as a marker of BER/SSBR processes, in real time to sites of DNA damage induced by sparsely ionizing radiation in mammalian cells
Summary
Cellular metabolism produces a number of reactive oxygen species (ROS) that can be neutralized by superoxide dismutase, catalases and glutathione peroxidases [1]. Some ROS may persist and DNA is one of the cellular targets for these highly reactive species, leading to the formation of a number of DNA lesions, abasic (AP) sites and single strand breaks (SSBs). In short patch BER (SP-BER), DNA polymerase  (Pol ) inserts a base into the resulting SSB [20,21] followed by ligation with ligase III. PARP1 is involved in SSBR through binding to SSBs with high affinity [27] followed by auto-modification to form polyADPribose (PAR) chains [28] These PAR chains are required for the recruitment of proteins, including XRCC1, and for the detachment of PARP1 from the damage site [29]
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