碱基切除修复（AP位点修复）
中文名称
通路描述
AP位点的修复可通过单核苷酸替换途径或多核苷酸补丁替换途径（即长补丁BER）发生。除APEX1介导的单核苷酸BER外，单核苷酸和多核苷酸补丁替换途径均由APEX1介导的DNA糖基化酶位移和APEX1在AP位点5'侧切割受损DNA链启动。BER通过单核苷酸替换途径进行，当APEX1产生的单链断裂（SSB）5'端的AP脱氧核糖残能被DNA聚合酶β（POLB）的5'-外切酶活性移除时，POLB通过向SSB 3'端添加与未受损DNA链互补的核苷酸来填补单核苷酸缺口。随后，DNA连接酶III（LIG3）在XRCC1与POLB的相互作用下，通过XRCC1介导的与POLB的相互作用被招募至BER位点。当AP残基在APEX1产生的SSB 5'端发生氧化相关损伤（5'ddRP）且无法被POLB切割时，BER通过多核苷酸补丁替换途径进行。长补丁BER可由PARP1或PARP2、FEN1和DNA连接酶I（LIG1）介导的DNA链置换合成完成。当PCNA-containing复制复合物可用（如细胞周期S期）时，DNA链置换合成由DNA聚合酶δ（POLD）或DNA聚合酶ε（POLE）复合物催化，在PCNA、RPA、RFC、APEX1、FEN1和LIG1存在下发生。9-1-1修复复合物（由HUS1、RAD1和RAD9组成）可能参与BER并协调其组件，但确切机制和时间尚未阐明。
英文描述
APEX1-Independent Resolution of AP Sites via the Single Nucleotide Replacement Pathway NEIL1 and NEIL2 have a dual DNA glycosylase and beta/delta lyase activity. The AP (apurinic/apyrimidinic) site-directed lyase activity of NEIL1 and NEIL2 is their major physiological role, as they can act on AP sites generated spontaneously or by other DNA glycosylases. NEIL1 or NEIL2 cleave the damaged DNA strand 5' to the AP site, producing a 3' phosphate terminus (3'Pi) and a 5' deoxyribose phosphate terminus (5'dRP). DNA polymerase beta (POLB) excises 5'dRP residue but is unable to add the replacement nucleotide to DNA with the 3'Pi end. PNKP, a DNA 3' phosphatase, removes 3'Pi and enables POLB to incorporate the replacement nucleotide, which is followed by ligation of repaired DNA strand by XRCC1:LIG3 complex (Whitehouse et al. 2001, Wiederhold et al. 2004, Das et al. 2006).
所含基因
7 个基因