A New XRCC1-Containing Complex and Its Role in Cellular Survival of Methyl Methanesulfonate Treatment

• DOI: 10.1128/mcb.24.19.8356-8365.2004
• Publication Date: 2004-09-14T19:58:18Z
• Authors: Hao Luo; Doug W. Chan; Tao Yang; Maria Rodriguez; Benjamin Ping-Chi...; Mei Leng; Jung-Jung Mu; David Chen; Zhou Songyang; Yi Wang; Jun Qin
• Keywords: XRCC1; Methyl methanesulfonate; DNA polymerase beta

DNA single-strand break repair (SSBR) is important for maintaining genome stability and homeostasis. The current SSBR model derived from an in vitro-reconstituted reaction suggests that the complex mediated by X-ray cross-complementing protein 1 (XRCC1) assembled sequentially at site of damage. In this study, we provide biochemical data to demonstrate two preformed XRCC1 complexes exist cycling HeLa cells. One contains known enzymes are SSBR, including ligase 3 (DNL3), polynucleotide kinase 3'-phosphatase, polymerase beta; other a new DNL3 ataxia with oculomotor apraxia type (AOA) gene product aprataxin. We report characterization complex. phosphorylated vivo vitro CK2, CK2 phosphorylation on S518, T519, T523 largely determines aprataxin binding though its FHA domain. An acute loss small interfering RNA renders cells sensitive methyl methanesulfonate treatment mechanism shortened half-life XRCC1. Thus, plays role maintain steady-state level Collectively, these insights into molecular machinery cell point involvement thus linking neurological disease AOA.