Objective To investigate the molecular mechanism and function of X-ray repair cross complementing 6(XRCC6)reg-ulate Ring1 and YY1 binding protein(RYBP)expression.Methods The interaction between XRCC6 and RYBP was analyzed by protein co-immunoprecipitation and immunofluorescence assays.The effect of XRCC6 on RYBP protein level was determined by Western blot-ting.The influence of XRCC6 on the stability of RYBP was detected by Western blotting and protein co-immunoprecipitation assays.Re-al-time fluorescence quantitative polymerase chain reaction(RT-qPCR)was used to determine whether XRCC6 regulates gene expres-sion through RYBP.Results There was an interaction between endogenous RYBP and XRCC6,and XRCC6 negatively regulated the lev-el of RYBP protein.Overexpression of XRCC6 promoted polyubiquitination and proteasome degradation of RYBP,and significantly short-ened its half-life.Furthermore,XRCC6 negatively regulated H2AK119Ub1 level and inhibited downstream gene expressions through modulating RYBP.Conclusion XRCC6 interacts with and down-regulates RYBP expression through proteasome pathway,thereby regu-lating the expression of RYBP downstream genes.

Objective To investigate the molecular mechanism and function of X-ray repair cross complementing 6(XRCC6)reg-ulate Ring1 and YY1 binding protein(RYBP)expression.Methods The interaction between XRCC6 and RYBP was analyzed by protein co-immunoprecipitation and immunofluorescence assays.The effect of XRCC6 on RYBP protein level was determined by Western blot-ting.The influence of XRCC6 on the stability of RYBP was detected by Western blotting and protein co-immunoprecipitation assays.Re-al-time fluorescence quantitative polymerase chain reaction(RT-qPCR)was used to determine whether XRCC6 regulates gene expres-sion through RYBP.Results There was an interaction between endogenous RYBP and XRCC6,and XRCC6 negatively regulated the lev-el of RYBP protein.Overexpression of XRCC6 promoted polyubiquitination and proteasome degradation of RYBP,and significantly short-ened its half-life.Furthermore,XRCC6 negatively regulated H2AK119Ub1 level and inhibited downstream gene expressions through modulating RYBP.Conclusion XRCC6 interacts with and down-regulates RYBP expression through proteasome pathway,thereby regu-lating the expression of RYBP downstream genes.