染色质改构复合物SRCAP在同源重组修复中的功能与作用机制

同源重组修复是细胞内最重要的DNA损伤修复方式之一。同源重组修复缺陷会导致基因组不稳定及多种疾病包括肿瘤的发生。DNA end resection是同源重组修复的关键步骤。最近我们发现SRCAP染色质改构复合物通过促进CtIP蛋白的招募参与DNA end resection起始以及同源重组修复。和很多参与DNA损伤应答的蛋白一样，在DNA发生损伤后，SRCAP也能够被招募到DNA损伤位点。但是，SRCAP染色质改构复合物被招募到DNA损伤位点的分子机制还不清楚。本研究旨在探索SRCAP染色质改构复合物是如何被招募到DNA损伤位点从而参与DNA end resection起始和同源重组修复。我们希望通过该研究进一步阐明SRCAP染色质改构复合物在DNA end resection及同源重组修复中的作用机制，并以期解释SRCAP突变导致Floating-Harbor syndrome的原因。

The repair of double-strand breaks (DSBs) in DNA by homologous recombination (HR) requires 5'-3' resection of the DNA ends. DNA-end resection is initiated by the collaborative action of CtIP together with the MRE11 nuclease complex. Recently We have demonstrated that the human SRCAP chromatin remodeling complex facilitates chromatin relaxation, thereby promoting accumulation of CtIP at sites of DNA damage and the subsequent CtIP-dependent DNA-end resection. However, the mechanism by which SRCAP is recruited to DNA damage sites remains elusive. In this study, we aim to gain further insights into the regulation of SRCAP upon DNA damage. A successful completion of this study will not only provide new insights into the molecular mechanisms that regulate DNA-end resection and homologus recombination, but also give us a deeper understanding of the molecular basis of Floating-Harbor syndrome.