Responsibility’s upon you and me (4)
I believe the answer is:
onus
'responsibility's' is the definition.
(onus is a duty or responsibility)
'upon you and me' is the wordplay.
'upon' becomes 'on' (I've seen this in other clues).
'you and me' becomes 'us'.
'on'+'us'='ONUS'
(Other definitions for onus that I've seen before include "albatross?" , "Encumbrance" , "'Burden, load (4)'" , "Weight of responsibility" , "'Responsibility, task or burden (4)'" .)