Updated at 3:36 p.m. ET

Sen. John McCain may, once again, be the savior of President Barack Obama's signature domestic achievement.

The Arizona Republican announced in a statement on Friday that he opposes the latest GOP legislation to dismantle the Affordable Care Act.

"I cannot in good conscience vote for the Graham-Cassidy proposal. I believe we could do better working together, Republicans and Democrats, and have not yet really tried," McCain said in a statement posted on his website.

McCain now joins Sen. Rand Paul, R-Ky., as one of two Republican "no" votes on the bill. Republicans cannot lose any additional senators and still pass the legislation with 50 votes and Vice President Pence acting as the tiebreaker.

One of the bill's sponsors, Sen. Lindsey Graham, R-S.C., is McCain's closest friend in the Senate and said that friendship "is not based on how he votes but respect for how he's lived his life and the person he is." Graham also vowed to "press on" with his legislation.

Senate Democratic leader Chuck Schumer said in a statement: "John McCain shows the same courage in Congress that he showed when he was a naval aviator. I have assured Senator McCain that as soon as repeal is off the table, we Democrats are intent on resuming the bipartisan process." An effort by GOP Sen. Lamar Alexander and Democratic Sen. Patty Murray, who lead the Senate Health, Education, Labor and Pensions Committee, has been put on hold since the Graham-Cassidy bill emerged.

The focus now shifts to two female GOP moderates, Sens. Lisa Murkowski of Alaska and Susan Collins of Maine, who joined McCain in ending the last GOP repeal bill in July.

Collins is widely believed to be opposed to Graham-Cassidy, as she has voted against all previous versions of GOP repeal bills, but she has not yet made her position on this bill public. She has, however, criticized Graham-Cassidy and echoed McCain's calls for bipartisan efforts to address health care concerns. At an event in Portland, Maine, on Friday morning, she said she was "leaning against the bill," according to the Portland Press Herald.

Likewise, Murkowski voted against the previous GOP health care bills and has not yet declared her position. The Trump administration and GOP Senate leaders have been in ongoing negotiations to try to win her vote.

If one of the two senators announces opposition to the latest bill, it cannot pass the Senate. GOP leaders have said this is the last attempt they will make to repeal Obamacare ahead of the Sept. 30 deadline, when special budget rules expire that allow Republicans to pass a bill with just 50 votes.

The bill, authored by Sens. Lindsey Graham of South Carolina and Bill Cassidy of Louisiana, is the most far-reaching GOP proposal to date to undo Obamacare. The bill repeals key pillars of the law, such as the individual mandate; loosens its federal regulations, like those affecting pre-existing conditions; and fundamentally overhauls Medicaid, changing it from an open-ended federal guarantee to a program of capped funding directly to the states.

McCain said his opposition is based not on the substance of the bill but rather how it was put together. "I would consider supporting legislation similar to that offered by my friends Senators Graham and Cassidy were it the product of extensive hearings, debate and amendment. But that has not been the case," he said.

McCain cast the decisive vote back in July that derailed an earlier version of the party's health care bill. His vote came just days after he was diagnosed with a severe form of brain cancer, for which he is undergoing chemotherapy and radiation treatments at the National Institutes of Health.

Paul's opposition to the bill is based on the Kentucky Republican's belief that it does not truly repeal the Affordable Care Act. "I won't vote for Obamacare Lite that keeps 90% of the taxes & spending just so some people can claim credit for something that didn't happen," Paul tweeted on Friday. Under pressure from Trump and other Republicans to change his mind, Paul added, "I won't be bribed or bullied."

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